Experimental characterization of SiCH+via single-photon ionization of gas-phase SiCH.

SiCH and its cation have consistently emerged as predicted species in models of silicon chemistry within the interstellar medium, although they remain unobserved in space. Hindered by their intrinsic instability, no spectroscopic insights have been gleaned concerning the SiCH+ cation. In this study, we present experimental measurements on the SiCH+ cation through single-photon ionization spectroscopy of the SiCH radical within the 8.0-11.0 eV range. Gas-phase SiCH radicals were generated through chemical reactions involving CHx (x = 0-3) and SiHy (y = 0-3) within a microwave discharge flow-tube reactor. Employing a double imaging photoelectron/photoion coincidence spectrometer on the DESIRS beamline at the SOLEIL synchrotron, we recorded mass-selected ion yield and photoelectron spectra. From the analysis of the photoelectron spectrum supported by ab initio calculations and Franck-Condon simulations, the adiabatic ionization energies for the transitions from the X2Π ground electronic state of SiCH toward the X+3Σ- and A+3Π electronic states of SiCH+ have been derived [8.935(6) and 10.664(6) eV, respectively, without spin-orbit correction]. The contribution from the less stable isomer HSiC has been explored in our analysis and ruled out in our experiments.

[Effect of high flow nasal catheter oxygen to prevent hypoxemia in endoscopic retrograde cholangiopancreatography surgery in aged].

Objective: To explore the effect of high-flow nasal catheter oxygen inhalation in preventing hypoxemia during endoscopic retrograde cholangiopancreatography (ERCP) surgery in elderly patients. Methods: From September 2021 to September 2022, 116 elderly patients (aged ≥ 70 years) who underwent elective ERCP in the Northern Theater General Hospital were prospectively selected, then divided into general nasal catheter oxygen inhalation group [group C, 31 males and 27 females, aged (79.8±6.4) years] and high-flow nasal catheter oxygen inhalation group [group H, 33 males and 25 females, aged (81.4±6.7) years], with 58 patients in each group. All patients were monitored for anesthesia by target-controlled infusion of propofol and remifentanil. The main outcome index was the incidence of intraoperative subclinical hypoxemia (90% ≤ SpO2 < 95%, duration >5 s), hypoxemia (75% < SpO2 < 90%, 5 s < duration ≤ 60 s) and severe hypoxemia (SpO2 < 75% or SpO2 < 90%, duration > 60 s). Secondary observation measures were SpO2 from T0 to T5 (T0, before anesthesia induction; T1, immediately after anesthesia induction; T2, endoscopic introduction; T3, duodenal papula intubation; T4, endoscopic withdrawal; T5, postoperative awakening), the arterial oxygen partial pressure (PaO2), carbon dioxide partial pressure (PaCO2) and pH at T0, 15 min after the induction and T5. Results: The incidence of intraoperative subclinical hypoxemia in group C and group H was 12.0% (7/58) and 3.4% (2/58) respectively, which showed no significant statistical difference (P=0.165) from each other. The incidence of intraoperative hypoxemia in group H was 8.6% (5/58), which was significantly lower than 31.0% (18/58) of group C (P=0.003). Neither group had intraoperative severe hypoxemia. SpO2 of group H were (98.2±0.9)%, (98.2±0.9)%, (97.8±1.7)% and (97.7±1.7)% at T1, T2, T3, T4, which were higher than (96.8±2.1)%, (96.4±3.0)%, (96.1±2.9)% and (96.4±3.4)% in group C (all P<0.05). PaO2 at 15 min after induction in group H was (240.5±46.7) mmHg (1 mmHg=0.133 kPa), which was higher than that of group C (170.6±33.4) mmHg (P<0.001). There was no statistically significant difference in pH and PaCO2 between the two groups of patients at each timepoint. Conclusion: High flow nasal catheter oxygen can effectively reduce the incidence of hypoxemia in ERCP in elderly patients.

[Pan-cancer analysis of ubiquitin-specific protease 7 and its expression changes in the carcinogenesis of scar ulcer].

Objective: To explore the biological role and clinical significance of ubiquitin-specific protease 7 (USP7) in the carcinogenesis of scar ulcer. Methods: A retrospective observational study combined with bioinformatics analysis was used. The RNA expression profile data of USP7 in tumor and/or its corresponding paracancular normal tissue were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus database, and the RNA sequencing data were transformed by log2. The variations of USP7 gene were analyzed by cBioPortal database. The USP7 mRNA expression in tumor and adjacent normal tissue in TCGA database were obtained by using the "Gene_DE" module in TIMER 2.0 database. The survival rates of patients with high and low USP7 expression in cutaneous melanoma (SKCM), cervical squamous cell carcinoma (CESC), lung squamous cell carcinoma (LUSC), and head and neck squamous cell carcinoma (HNSC) were analyzed using the Gene Expression Profile Interactive Analysis 2 (GEPIA2) database, and the Kaplan-Meier survival curves were drawn. Sangerbox database was used to analyze the correlation of USP7 expression in pan-cancer with microsatellite instability (MSI) or tumor mutation burden (TMB) pan-cancer. Through the "correlation analysis" module in the GEPIA2 database, the correlation of USP7 expression in pan-cancer with the expression levels of five DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) and three essential DNA methyltransferases (DNMT)--DNMT1, DNMT3A, and DNMT3B were evaluated. The USP7 expression in CESC, HNSC, LUSC, and SKCM and its correlation with infiltration of immune cells (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) were analyzed by the "Immune-Gene" module in TIMER 2.0 database. The "Similar Genes Detection" module of GEPIA2 database was used to obtain the top 100 protein sets with similar expression patterns to USP7. Intersection analysis was performed between the aforementioned protein sets and the top 50 protein sets that were directly physically bound to USP7 obtained by using the STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were performed for the two protein sets mentioned above using the DAVID database. The samples of normal skin, hypertrophic scar, scar ulcer, and scar carcinoma with corresponding clinicopathologic features were collected from the Department of Pathology of Tongren Hospital of Wuhan University & Wuhan Third Hospital from October 2018 to October 2022, and the USP7 expression in tissue was detected by immunohistochemical method, with the number of samples of 6. Data were statistically analyzed with Log-rank test, one-way analysis of variance, and Bonferroni test. Results: In pan-cancer, the main gene variations of USP7 were mutation and amplification, and the top 3 tumors with the highest variation frequency (>6%) were bladder urothelial carcinoma, SKCM, and endometrial carcinoma. The main mutation of USP7 gene in pan-cancer was missense mutation. In SKCM with the highest mutation frequency, the main type of mutation was missense mutation in USP7_ICP0_bdg domain. USP7 mRNA expression in breast invasive carcinoma, bile duct carcinoma, colon carcinoma, esophageal carcinoma, HNSC, renal chromophobe cell carcinoma, hepatocellular carcinoma, lung adenocarcinoma, LUSC, prostate carcinoma, and gastric carcinoma was significantly higher than that in corresponding paracancer normal tissue (P<0.05). USP7 mRNA expression in glioblastoma multiforme, renal clear cell carcinoma, renal papillary cell carcinoma, and thyroid carcinoma was significantly lower than that in corresponding paracancular normal tissue (P<0.05). In addition, USP7 mRNA expression in SKCM metastases was much higher than that in primary tumor tissue (P<0.05). Survival curves showed no significant difference in survival rate between patients with high USP7 expression and patients with low USP7 expression in CESC, HNSC, LUSC, and SKCM (Log-rank P>0.05, with hazard ratios of 1.00, 0.99, 1.00, and 1.30, respectively). USP7 expression in colon cancer, colorectal cancer, thymic cancer, and thyroid cancer was negatively correlated with TMB (with Pearson correlation coefficients of -0.26, -0.19, -0.19, and 0.11, respectively, P<0.05). USP7 expression in glioma, CESC, lung adenocarcinoma, mixed renal carcinoma, and LUSC was positively correlated with MSI expression (with Pearson correlation coefficients of 0.22, 0.14, 0.15, 0.08, and 0.14, respectively, P<0.05), and USP7 expression in colon cancer, colorectal cancer, invasive breast cancer, prostate cancer, HNSC, thyroid cancer, and diffuse large B-cell lymphoma were significantly negatively correlated with MSI expression (with Pearson correlation coefficients of -0.31, -0.27, -0.13, -0.19, -0.16, -0.18, and -0.53, respectively, P<0.05). The expression of USP7 in CESC was positively correlated with that of both MSH2 and MSH6 (with Spearman correlation coefficients of 0.51 and 0.44, respectively, P<0.05), and the expression of USP7 in HNSC was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.39, 0.14, 0.49, 0.54, and 0.41, respectively, P<0.05), and the expression of USP7 in LUSC was positively correlated with the expression of EPCAM, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.20, 0.36, 0.40, and 0.34, respectively, P<0.05), and the expression of USP7 in SKCM was positively correlated with the expression of EPCAM, MLH1, MSH2, MSH6, and PMS2 (with Spearman correlation coefficients of 0.11, 0.33, 0.42, 0.55, and 0.34, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was significantly positively correlated with the expression of DNMT1, DNMT3A, and DNMT3B (with Spearman correlation coefficients of 0.42, 0.34, 0.22, 0.45, 0.52, 0.22, 0.36, 0.36, 0.22, 0.38, 0.46, and 0.21, respectively, P<0.05). The expression of USP7 in CESC, HNSC, LUSC, and SKCM was positively correlated with CD4+ T cell infiltration (with Partial correlation coefficients of 0.14, 0.22, 0.13, and 0.16, respectively, P<0.05). Being similar to the pattern of USP7 expression and ranked among top 100 protein sets, the top 5 proteins were C16orf72, BCLAF1, UBN, GSPT1, ERI2 (with Spearman correlation coefficients of 0.83, 0.74, 0.73, and 0.72, respectively, all P values<0.05). The top 50 protein sets that directly physically bind to USP7 overlapped with the aforementioned protein set by only one protein, thyroid hormone receptor interaction factor 12. KEGG enrichment analysis showed that USP7 related genes were involved in cell cycle, spliceosome, cell senescence, and p53 signal pathway. GO enrichment analysis showed that USP7 related genes were involved in transcriptional regulation, protein ubiquitination, DNA repair, and cytoplasmic pattern recognition receptor signal pathways. Analysis of clinical samples showed that USP7 expression was significantly higher in hypertrophic scars (0.35±0.05), scar ulcers (0.43±0.04), and scar cancers (0.61±0.03) than in normal skin (0.18±0.04), P<0.05. Conclusions: USP7 may be a clinical biomarker for the progression of cicatricial ulcer cancer.

Single-photon ionization of SiC in the gas phase: experimental and ab initio characterization of SiC.

We report the first experimental observation of single-photon ionization transitions of the SiC radical between 8.0 and 11.0 eV performed on the DESIRS beamline at the SOLEIL synchrotron facility. The SiC radical, very difficult to synthesize in the gas phase, was produced through chemical reactions between CHx (x = 0-3) and SiHy (y = 0-3) in a continuous microwave discharge flow tube, the CHx and SiHy species being formed by successive hydrogen-atom abstractions induced by fluorine atoms on methane and silane, respectively. Mass-selected ion yield and photoelectron spectra were recorded as a function of photon energy using a double imaging photoelectron/photoion coincidence spectrometer. The photoelectron spectrum enables the first direct experimental determinations of the X+ 4Σ- ← X 3Π and 1+ 2Π â† X 3Π adiabatic ionization energies of SiC (8.978(10) eV and 10.216(24) eV, respectively). Calculated spectra based on Franck-Condon factors are compared with the experimental spectra. These spectra were obtained by solving the rovibrational Hamiltonian, using the potential energy curves calculated at the multireference single and double configuration interaction level with Davidson correction (MRCI + Q) and the aug-cc-pV5Z basis set. MRCI + Q calculations including the core and core-valence electron correlation were performed using the aug-cc-pCV6Z basis set to predict the spectroscopic properties of the six lowest electronic states of SiC+. Complete basis set extrapolations and relativistic energy corrections were also included in the determination of the energy differences characterizing the photoionization process. Using our experimental and theoretical results, we derived semi-experimental values for the five lowest ionization energies of SiC.

[Efficacy of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion].

Objective: To analyze the treatment effects and side effects of non-surgical comprehensive treatment for locally advanced hypopharyngeal carcinoma invading cervical esophagus. Methods: A retrospective analysis was performed on sixty-six patients with locally advanced hypopharyngeal carcinoma invade the esophagus. These patients were treated in the Department of Otolaryngology, Head and Neck Surgery of Chinese People's Liberation Army General Hospital between January 2011 and May 2022, including sixty-five males and one female, aged 43-71 years. Treatment regimen consisted of induction chemotherapy and concurrent chemoradiothrapy and epidermal growth factor receptor (EGFR)-targeted therapy, three of these cases were treated with programmed cell death 1 (PD-1) immunotherapy. The Kaplan-Meier method was used for survival analysis. Side effects were evaluated with the established CTCAE (Common Terminology Criteria for Adverse Events) 5.0 criteria. The factors affecting prognosis were analyzed by Cox multivariate regression analysis. Results: Sixty-four (97.0%, 64/66) patients completed the radiotherapy and chemotherapy plan. The most common grade three side effects were radioactive oropharyngeal mucositis (89.1%, 57/64) and leukopenia (23.4%, 15/64). Five (7.8%, 5/64) patients showed grade three hoarseness; two patients (3.1%, 2/64) suffered from grade three swallowing dysfunction and required feeding tube and intravenous nutrition; the remaining patients(89.1%) retained good vocal and swallowing functions. The overall survival (OS) of all patients was 81.5% after one year, 54.0% after three years, and 39.9% after five years; the progression-free survival (PFS) was 78.3% after one year, 54.9% after three years, and 42.6% after five years; local control rate (LCR) was 80.9% after one year, 62.5% after three years, and 52.0% after five years. T4a patients showed better OS, PFS and LCR than T4b patients, with statistically significant differences (χ2=8.10, 8.27, and 6.64, respectively, all P<0.05). Cox multivariate regression analysis showed that lymph node metastasis was an independent factor affecting prognosis (χ2=10.21, P<0.05). Conclusion: Non-surgical comprehensive treatment can provide with another option of radical treatment for locally advanced hypopharyngeal carcinoma with cervical esophagus invasion, offering the patients higher rate of larynx and esophageal preservation with tolerable side effects.

[Endoscopic ultrasonographic features of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors and their correlation with progression and pathological risk grade of the lesions].

Objective: To investigate the endoscopic ultrasonographic (EUS) characteristics of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors (GIST) and their correlation with biological behaviors and pathological risk grade of the tumors. Methods: Retrospective cohort study. The EUS findings, follow-up review, surgical treatment and pathological data of patients with suspected GIST at the Gastrointestinal Endoscopy Center of Peking University People's Hospital from January 2013 to April 2021 were collected. All samples were divided into follow-up group and treatment group based on the pathological condition and the patient's treatment intention. According to whether or not the tumor was enlarged in EUS, the follow-up group was divided into non-enlarged group and enlarged group. Paired T-test was used to compare the lesion size before and after follow-up, and logistic regression was used to analyze the risk factors of tumor enlargement. According to the treatment methods, the treatment group was further divided into endoscopic treatment group and surgical treatment group. According to the pathological results and risk grade, the treatment group was further divided into the low-risk group and the medium-risk group. The risk factors of pathological malignant risk were analyzed by logistic regression, and the tumor diameter of patients with moderate or above pathological risk was predicted by receiver operation characteristic (ROC) curve. The relationship between the findings of EUS and the progression and pathological risk of GIST were also explored. Results: Seventy-three cases including 23 males and 50 females, with an age of 58 (30-88) years, were included in the follow-up group, with a mean lesion diameter of (1.21±0.49) cm before follow-up, median follow-up interval of 33.8 months, and a lesion diameter of (1.18±0.49) cm after follow-up. There was no significant difference (all P>0.05) in lesion diameter between before and after follow-up. There was no significant difference (all P>0.05) between tumor enlargement group (18 cases, 24.7%) and non-enlargement group (55 cases, 75.3%). One hundred and thirty-eight cases, including 52 males and 86 females, with an age of 60 (19-84) years, were enrolled in the treatment group, with a mean EUS estimated diameter of (2.55±1.35) cm and pathological diameters of (3.43±2.42) cm. Ninety-five (68.8%) of these cases were pathologically confirmed as GIST while 43 cases were diagnosed as other tumor types, including 37 benign tumors and 6 malignant tumors. In multifactorial logistic regression analysis, only the increase of tumor diameter [OR (95%CI): 1.800 (1.172-2.766), P=0.007] was a risk factor for pathological intermediate or higher risk. The optimal tumor diameter for predicting pathological intermediate or higher risk using ROC curve analysis was 2.75 cm, with a sensitivity 71.4%, specificity 79.0%, Youden index 0.5 and area under ROC curve 0.807 (95%CI: 0.703-0.909). Conclusions: EUS is essential for assessing the risk of progression and malignancy of submucosal lesions of upper digestive tract suspected GIST. For lesions of small diameter, the interval of follow-up shall be relatively extended while the indication of treatment could be partially waived.

[Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness].

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

Effect of arginine supplementation on the production of milk fat in dairy cows.

Arginine, one of the conditionally essential AA, has been reported to affect fat synthesis and metabolism in nonruminant animals by influencing adenosine monophosphate activated protein kinase (AMPK) in some organs. In dairy cows, the effect of Arg on milk fat production is not clear, and any potential mechanism that underlies the effect is unknown. We tested the hypothesis that Arg infusion would improve the production of milk fat, and explored possible mechanism that might underlie any effect. We used 6 healthy lactating cows at 20 ± 2 d in milk, in fourth parity, with a body weight of 508 ± 14 kg, body condition score of 3.0 ± 0, and a milk yield of 30.6 ± 1.8 kg/d (mean ± standard deviation). The cows were blocked by days in milk and milk yield and each cow received 3 treatments in a replicated 3 × 3 Latin square design, with each of the experimental periods lasting 7 d with a 14-d washout between each period. The treatments, delivered in random order, were (1) infusion of saline (control); (2) infusion of 0.216 mol/d of l-Arg in saline (Arg); (3) infusion of 0.868 mol/d of l-Ala in saline (the Arg and Ala treatments were iso-nitrogenous) through a jugular vein. On the last day of each experimental period, blood was sampled to measure insulin, nitric oxide, glucose, and nonesterified fatty acid, and the liver and mammary gland were biopsied to measure the expression of genes. Milk yield was recorded, and milk fat percentage was measured daily during each of the experimental periods. The yield and composition of fatty acid (FA) in milk was measured daily on the last 3 d during each of the experimental periods. The data were analyzed using a mixed model with treatment as a fixed factor, and cow, period, and block as random factors. The daily milk yield and milk fat yield when the cows were infused with Arg were 2.2 kg and 76 g, respectively, higher than that in control, and 1.8 kg and 111 g, respectively, higher than that in Ala. When the cows were infused with Arg they had higher concentration and yield of de novo synthesized FA, than when they received the control or Ala infusions, although milk fat percentage, daily feed intake, and the digestibility of nutrients were not affected by treatment. The serum concentration of nitric oxide and insulin were higher during Arg than during control or Ala, with no difference between control and Ala. In the liver, the expression of the genes coding for AMPK (PRKAA1, PRKAB1, and PRKAG1) and genes related to the oxidation of FA were higher during Arg than during control or Ala, whereas in the mammary gland the expression PRKAB1 was lowest, and the expression of genes involved in the synthesis of milk fat were highest, during Arg infusion. The results suggest the intravenous infusion of Arg enhanced the production of milk fat by promoting the de novo synthesis of FA and increasing milk yield.

Novel human-derived EML4-ALK fusion cell lines identify ribonucleotide reductase RRM2 as a target of activated ALK in NSCLC.

INTRODUCTION: Echinoderm microtubule-associated protein-like 4 (EML4)-Anaplastic Lymphoma Kinase (ALK) rearrangements occur in 3% to 7% of lung adenocarcinomas and are targets for treatment with tyrosine kinase inhibitors (TKIs). Here we have developed three novel EML4-ALK-positive patient-derived Non-Small-Cell-Lung-Cancer (NSCLC) cancer cell lines, CUTO8 (variant 1), CUTO9 (variant 1) and CUTO29 (variant 3) and included a fourth ALK-positive cell line YU1077 (variant 3) to study ALK-positive signaling and responses. Variants 1 and 3 are the most common EML4-ALK variants expressed in ALK-positive NSCLC, and currently cell lines representing these EML4-ALK variants are limited. MATERIALS AND METHODS: Resazurin assay was performed to evaluate cell viability. Protein levels were determined using western blotting. RNA sequencing was performed in all four cell lines to identify differentially expressed genes. Whole-genome sequencing was performed to determine the presence of EML4-ALK fusion and ALK tyrosine kinase inhibitor resistance mutations. RESULTS: In this study, we have confirmed expression of the corresponding ALK fusion protein and assessed their sensitivity to a range of ALK tyrosine kinase inhibitors. These patient derived cell lines exhibit differential sensitivity to lorlatinib, brigatinib and alectinib, with EML4-ALK variant 3 containing cell lines exhibiting increased sensitivity to lorlatinib and brigatinib as compared to alectinib. These cell lines were further characterized by whole genome sequencing and RNA-seq analysis that identified the ribonucleotide reductase regulatory subunit 2 (RRM2) as a downstream and potential therapeutic target in ALK-positive NSCLC. CONCLUSION: We provide a characterization of four novel EML4-ALK-positive NSCLC cell lines, highlighting genomic heterogeneity and differential responses to ALK TKI treatment. The RNA-Seq characterization of ALK-positive NSCLC CUTO8, CUTO9, CUTO29 and YU1077 cell lines reported here, has been compiled in an interactive ShinyApp resource for public data exploration (https://ccgg.ugent.be/shiny/nsclc_rrm2_2022/).

[Microfocal prostate cancer: a clinicopathological analysis of 206 cases].

Objective: To investigate the clinical and pathological features and prognosis of patients with microfocal prostate adenocarcinoma. Methods: Clinical and pathological data of the patients diagnosed with microfocal adenocarcinoma on prostate biopsy at the West China Hospital from 2013 to 2019 were collected. Microfocal adenocarcinoma was defined as follows: Gleason score of 3+3=6, total number of the cores ≥10, number of the positive cores ≤2, and proportion of the tumor in each positive core<50%. Clinicopathological parameters, treatment plans and follow-up data were collected. Pathological information of the biopsy and radical resection specimens was used to analyze the correlation between pathological parameters in the biopsy report and adverse pathological features of radical resection specimens, including increased Gleason score, capsule invasion, positive surgical margin and perineural invasion. Results: A total of 206 cases of microfocal adenocarcinoma were diagnosed on prostate biopsies from 2013 to 2019, accounting for 6.7% of all adenocarcinoma cases. There were 139 cases of 1 positive core and 67 cases of 2 positive cores. Patients with microfocal adenocarcinoma were younger than those with non-microfocal adenocarcinoma (69 years versus 71 years, P<0.001). Compared with patients with non-microfocal adenocarcinoma, the pre-biopsy total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) levels in patients with microfocal adenocarcinoma were both lower (11.2 µg/L2 versus 23.7 µg/L2; 1.4 µg/L2 versus 3.0 µg/L2, P<0.001), the fPSA/tPSA level was higher (12.9% versus 10.7%, P<0.05), the prostate volume was larger (38.9 mL versus 34.3 mL, P<0.05), and the PSA density was lower (0.3 µg/L2 versus 0.8 µg/L2, P<0.001). 130 patients underwent radical prostatectomy, 30 patients chose active monitoring, 31 patients chose endocrine or radiation therapy, and 15 patients were lost to follow-up. Three patients in the active surveillance group underwent radical prostatectomy for disease progression after 21-39 months observation. Biochemical relapses occurred in two patients in the radical prostatectomy group. The remaining patients have no disease progression or recurrence at present. Compared with radical prostatectomy specimens, Gleason score in the biopsy material was increased in 64/115 patients (55.7%). Among resection excision specimens, 14 cases (12.2%) had extraprostatic extension (EPE), 35 cases (30.4%) had perineural invasion, and 16 cases (13.9%) had a positive margin. Univariate and multivariate analyses showed that low fPSA/tPSA ratio and 2 positive cores were independent risk factors for Gleason score increase in the radical prostatectomy specimens. A low fPSA/tPSA ratio was an independent risk factor for perineural invasion. Low fPSA/tPSA ratio and low prostate volume were associated with a positive margin in radical prostatectomy specimens. Conclusions: In this study, patients diagnosed with microfocal adenocarcinoma on prostate biopsy account for a high proportion of the patients with increased Gleason score in the radical prostatectomy specimens, and there is a certain proportion of adverse pathological features in the radical specimens. Therefore, for the patients with only a small amount of low-grade adenocarcinoma found in biopsy, PSA levels and PSA density should be taken into consideration in treatment selection.

[Research on emergency management and legal system of occupational disease accidents in China].

A great deal of work has carried out and get some achieved in the construction of emergency management and legal system for dealing with occupational disease accidents in China, however, the governance of occupational disease accidents is still weak in occupational health management. Based on the analysis of the situation of occupational disease accident emergency management and legal system construction at home and abroad, this paper summarizes the problems existing in the governance of occupational disease accidents, such as the need to further define the connotation and extension, the need to improve the regulations and policies, and the need to establish and improve the emergency management system. It is considered that it is very important to carry out research on the scientific definition, classification and management of occupational disease accidents.

[Outcomes of patients experiencing cardiovascular adverse events within 1 year following craniotomy for intracranial aneurysm clipping: a retrospective cohort study].

OBJECTIVE: To investigate the impact of postoperative serious cardiovascular adverse events (CAE) on outcomes of patients undergoing craniotomy for intracranial aneurysm clipping. METHODS: This retrospective cohort study was conducted among the patients undergoing craniotomy for intracranial aneurysm clipping during the period from December, 2016 to December, 2017, who were divided into CAE group and non-CAE group according to the occurrence of Clavien-Dindo grade ≥II CAEs after the surgery. The perioperative clinical characteristics of the patients, complications and neurological functions during hospitalization, and mortality and neurological functions at 1 year postoperatively were evaluated. The primary outcome was mortality within 1 year after the surgery. The secondary outcomes were Glasgow outcome scale (GOS) score at 1 year, lengths of postoperative hospital and intensive care unit (ICU) stay, and Glasgow coma scale (GCS) score at discharge. RESULTS: A total of 361 patients were enrolled in the final analysis, including 20 (5.5%) patients in CAE group and 341 in the non-CAE group. No significant differences were found in the patients' demographic characteristics, clinical history, or other postoperative adverse events between the two groups. The 1-year mortality was significantly higher in CAE group than in the non-CAE group (20.0% vs 5.6%, P=0.01). Logistics regression analysis showed that when adjusted for age, gender, emergency hospitalization, subarachnoid hemorrhage, volume of bleeding, duration of operation, aneurysm location, and preoperative history of cardiovascular disease, postoperative CAEs of Clavien-Dindo grade≥II was independently correlated with 1-year mortality rate of the patients with an adjusted odds ratio of 3.670 (95% CI: 1.037-12.992, P=0.04). The patients with CEA also had a lower GOS score at 1 year after surgery than those without CEA (P=0.002). No significant differences were found in the occurrence of other adverse events, postoperative hospital stay, ICU stay, or GCS scores at discharge between the two groups (P > 0.05). CONCLUSION: Postoperative CAEs may be a risk factor for increased 1-year mortality and disability in patients undergoing craniotomy for intracranial aneurysms.

[Retrospective analysis on 77 cases of T4b hypopharyngeal carcinoma treated by non-surgical treatments].

Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.

[Identification and validation of hub genes in prostate cancer progression based on weighted gene co-expression network analysis].

OBJECTIVE: To identify the key hub genes in prostate cancer metastasis based on weighted gene co-expression network analysis (WGCNA) and verify the identified genes. METHODS: Whole-genome chip data GSE6919 of prostate cancer study were analyzed using principal component analysis (PCA), and the differentially expressed genes (DEGs) were analyzed using R software. WGCNA was performed to construct a gene co-expression network for screening the key genes. TCGA database was used to explore the expressions of the DEGs and their association with the prognosis. To validate the results, we designed siRNA fragments targeting the metastasis-related gene HNRNPA2B1, and observed its effect on growth, apoptosis, clone formation, migration and invasion of prostate cancer cell lines using MTT assay, flow cytometry, clone formation assay, and Transwell assay. RESULTS: PCA analysis showed obvious clustering of significant DEGs in metastatic cancer group. The modules obtained by WGCNA analysis in metastasis group involved stem cell differentiation, amino acid metabolism and immune response. Further screening of the genes identified 3 genes related with prostate cancer occurrence (BDH1, PAK4 and EXTL3) and another 3 with prostate cancer metastasis (NKTR, CTBP2 and HNRNPA2B1), which were shown to have differential expressions in TCGA database and were correlated with the patient's overall survival. In the cell experiment, PC3 and LNCap cells transfected with the siRNA fragment targeting HNRNPA2B1 showed obvious growth inhibition with increased cell apoptosis, lowered clone formation ability, and suppressed capacities for migration and invasion. CONCLUSION: We identified 3 hub genes related with the occurrence (BDH1, PAK4 and EXTL3) and another 3 with metastasis of prostate cancer (NKTR, CTBP2 and HNRNPA2B1) using WGCNA, which provides a new approach for studying the regulatory mechanisms of prostate cancer.

[Management algorithm for septic arthritis after anterior cruciate ligament reconstruction].

OBJECTIVE: To summarize the experience in the diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction. METHODS: A retrospective review was conducted of all the arthroscopic anterior cruciate ligament reconstructions performed at Department of Sports Medicine, Peking University Third Hospital between January 2001 and December 2020. In the study, 65 of 27 867 patients experienced postoperative septic arthritis. The incidence, presentation, laboratory results, treatment, and outcome of all the infected patients were analyzed. The experiences of diagnosis and management of septic arthritis after anterior cruciate ligament reconstruction were summarized. RESULTS: A total of 27 867 anterior cruciate ligament reconstructions were performed at our department between January 2001 and December 2020. In the study, 65 (0.23%) patients were identified with postoperative septic arthritis. The most common symptoms of the infected patients were fever (38.7±0.5) ℃, knee swelling, pain, and restricted motion. The mean peripheral white blood cell count (WBC) was (9.2±2.6)×109/L (range 4.2×109/L-19.4×109/L), with (72.5±6.3) % (range 54.9%-85.1%) polymorphonuclear neutrophils (N). The mean erythrocyte sedimentation rate (ESR) was (59.9±24.1) mm/h (range 9-108 mm/h), C-reactive protein (CRP) was (10.9±5.7) mg/dL (range 1.2-30.8 mg/dL), and fibrinogen (FIB) level was (7.0±1.6) g/L (range 3.7-10.8 g/L). All of the laboratory results were statistically higher in the infection group compared with the normal postoperative group (P＜0.001). The synovial white blood cell count (SWBC) of aspirated knee joint fluid was (45.0±29.8)×109/L (range 7.1×109-76.5×109/L). Polymorphonuclear cell percentage (PMNC) was (90.27±7.86) % (range 60%-97%). In the study, 45 patients (69.2%) had positive aspirate cultures. Microbiology showed coagulase-negative Staphylococcus (CNS) and Staphylococcus aureus (SA) were the most common bacterium (34 cases and 7 cases, individually). There were 26 methicillin-resistant Staphylococcus. Both conservative (16 patients) and operative (49 patients) treatments were effective, but conservative group had a longer recovery time (5.6 d vs. 1.6 d, P=0.042). CONCLUSION: Septic arthritis after arthroscopic anterior cruciate ligament reconstruction is a rare but potentially devastating complication. The correct diagnosis relies on synovial fluid analysis and bacterial culture. Our proposed treatment protocol is arthroscopic debridement and antibiotic therapy as quickly as possible.

[Clinicopathological features of adenocarcinoma of the rete testis].

Objective: To investigate the clinicopathological features, immunophenotype, and differential diagnosis of adenocarcinoma of the rete testis. Methods: Four adenocarcinoma cases of the rete testis diagnosed at West China Hospital, Chengdu, China (3 cases, including 2 consultation cases) and the First Affiliated Hospital of Fujian Medical University, Fuzhou, China (1 case) between January 2009 and December 2017 were included. Their clinical, morphologic and immunohistochemical features were analyzed using histological analysis and immunohistochemical staining. Related literature was reviewed to reveal the characteristics of this tumor. Results: The 4 patients' age range was 26-64 years. The maximum diameters of the tumors were 3.0 and 4.5 cm in 2 cases, respectively. On gross examination, adenocarcinomas of the rete testis appeared as a solid, white to gray or tan to yellow mass that raised at the hilum of the testis. Microscopically, all tumors showed multiple histologic patterns, including corded/trabecular (4/4), glandular, nested, sarcomatoid (3/4), solid (2/4), papillary, cribriform, and slit-like (1/4). Three types of adenocarcinoma cells included cuboidal to columnar (4/4), polygonal (4/4) and spindle-shaped (2/4) with pale eosinophilic and clear cytoplasm. The tumor cell nuclei appeared moderately to markedly atypical and pleomorphic, with a various number of mitoses. Transition from benign to malignant rete epithelium was seen in all cases. Eosinophilic hyaloid globules were found in 1 case. On immunohistochemical study, the tumor cells were diffusely, strongly positive for CKpan (4/4), EMA (4/4), Ber-EP4 (3/3) and CAⅨ(2/2), and focally positive for CK7 (4/4), vimentin (4/4), CD10 (4/4), PAX8 (3/3), PAX2 (3/3). The Ki-67 proliferative index was all>50% (4/4). The prognosis was poor. Two of the 3 patients died within 1 year after the surgical resection. Conclusions: Adenocarcinoma of the rete testis is a rare malignant tumor with several histologic patterns. Transition from benign to malignant rete epithelium is an important diagnostic clue. Detailed clinical history, tumor growth site and immunohistochemistry are helpful for its diagnosis and differential diagnosis.