[Screening and validation of therapeutic targets for chronic sinusitis with nasal polyps based on proteomics].

Objective: To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally. Methods: The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software. Results: DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group (P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion: The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.

[Clinical features and prognostic analysis of colorectal extranodal NK/T cell lymphoma].

Objective: To investigate the clinical manifestations, endoscopic characteristics, and prognostic factors of patients with colorectal extranodal NK/T cell lymphoma. Methods: The clinical data of 52 patients with colorectal extranodal NK/T cell lymphoma admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to January 2023 were retrospectively analyzed. Their clinical manifestations and endoscopic characteristics were summarized, and the prognostic factors were analyzed by Cox regression model. Results: Among the 52 patients with colorectal extranodal NK/T cell lymphoma, there were 35 males and 17 females, with a male-to-female ratio of 2.06∶1. Among the general symptoms, abdominal pain was the most common (39 cases), and B symptoms occurred in 47 patients, among which fever was the most common lymphoma B symptom (42 cases), and gastrointestinal perforation was the most common complication (18 cases). Forty-three patients underwent colonoscopy, and the main manifestations under endoscopy were the ulceration type (24 cases). The ulcers were irregular at the edges and often covered with moss at the bottom. The median survival time was 4.3 months. Multivariate Cox regression analysis showed that hemocytic syndrome (HR=8.50,95% CI: 1.679-8.328,P=0.001), serum albumin (HR=3.59,95% CI: 1.017-6.551, P=0.048), and with or without chemotherapy (HR=0.31, 95% CI: 0.246-1.061, P=0.025) were independent factors influencing the overall survival of patients with colorectal extranodal NK/T cell lymphoma. Conclusions: Colorectal extranodal NK/T cell lymphoma is a rare disease with a very poor prognosis. When patients present with abdominal pain and lymphoma B symptoms, and when ulcers with irregular edges and moss covering the bottom are found under endoscopy, the disease should be considered, and endoscopic biopsy should be taken in time for pathological diagnosis. The prognosis of patients with hemophagocytic syndrome and hypoproteinemia is poor. This disease should be treated with chemotherapy and surgery, and on this basis, hemophagocytic syndrome and hypoproteinemia should be treated to improve the prognosis of patients.

Effect of manganese amino acid complexes on growth performance, meat quality, breast muscle and bone development in broilers.

1. This study was conducted to investigate the effects of dietary supplementation of manganese (Mn) amino acid complexes on growth performance, Mn deposition, meat quality, breast muscle and bone development of broilers.2. A total of 504, one-day-old male Arbor Acres broilers were randomly divided into seven treatments; control diet (CON; basal diet, no extra Mn addition), manganese diet (MnN as Numine®-Mn; CON + 40, 80, 120 or 160 mg Mn/kg), manganese-S group (MnS; CON + 120 mg Mn/kg as MnSO4·H2O), manganese-A diet (MnA as Mn from hydrolysed feather meal; CON + 40 mg Mn/kg as MnA).3. There were no significant differences for average daily gain (ADG) or feed intake (ADFI) among diets during the feed phases (p > 0.05). The FCR in the starter and over the whole period were quadratically affected by dietary MnN dosage and gave the lowest FCR at 80 mg/kg (p < 0.05). The Mn content of thigh muscle, jejunum, heart, pancreas, liver and tibia increased linearly with MnN addition (p < 0.05).4. For meat quality, MnN significantly increased colour (a*), pH45 min and pH24 h, reduced shear force, drip loss and pressure loss of breast muscle (p < 0.05).5. Moreover, MnN significantly upregulated MYOD expression at d 21 and SOD expression at d 42, decreased MuRF1 and Atrogin-1 mRNA level at d 42 in breast muscle. Transcriptome analysis revealed that the regulating effect of MnN on muscle development significantly enriched signalling pathways such as adhesion, ECM-receptor, MAPK, mTOR and AMPK. Furthermore, dietary MnN significantly affected tibia length and growth plate development (p < 0.05) and promoted growth plate chondrocytes by increasing SOX-9, Runx-2, Mef2c, TGF-ß, Ihh, Bcl-2 and Beclin1 and decreasing Bax and Caspase-3 (p < 0.05) expression which affect longitudinal tibial development.6. In conclusion, Mn amino acid complexes could improve growth performance, tissue Mn deposition, breast muscle development, meat quality and bone development.

Night shift work and myocardial infarction in the UK Biobank.

BACKGROUND: Shift work has become popular along with adverse effects such as disrupted biological rhythms, metabolic changes, sleep disorders and myocardial infarction. Studies have shown a link between myocardial infarction and shift work, but evidence is still lacking. AIMS: We aim to explore the association between present and past shift work and risk of myocardial infarction in a large population of European workers. METHODS: We analysed data from the UK Biobank with >500 000 participants and an average 12-year follow-up duration. Cox proportional hazard models were employed to analyse the relationship between present shift work (n = 265 064), lifetime duration or frequency of shift work (n = 71 428) and the risk of myocardial infarction, as well as the association between rest day during shift work and myocardial infarction incidents in night shift workers (n = 14 588). RESULTS: Night shift workers had a higher risk of myocardial infarction compared to day workers, including 'shift but never/rarely night shifts' (hazard ratio [HR] = 1.09, 95% confidence interval [CI] 1.00-1.20), 'some night shifts' (HR = 1.13, 95% CI 1.01-1.27) and 'usual/permanent night shifts' (HR = 1.21, 95% CI 1.07-1.37), respectively. Similarly, higher frequency and longer duration of night shift work were associated with the increased risk of myocardial infarction (<10 years: HR = 1.20, 95% CI 1.01-1.42; ≥10 years: HR = 1.51, 95% CI 1.28-1.77; or an average of more than eight nights per month: HR = 1.45, 95% CI 1.23-1.71). However, longer rest days couldn't decrease myocardial infarction risk compared to those who rest 1 day. CONCLUSIONS: Present and lifetime exposure to night shifts were associated with a risk of myocardial infarction and did not benefit from longer rest days.

Comparison of Efficacy and Safety of Different Second-line Therapies for Patients With Advanced Thymic Carcinoma.

AIMS: Thymic carcinoma (TC) is a rare form of highly invasive tumors. Currently, the standard first-line therapy involves paclitaxel plus carboplatin treatment, while the recommended regimen for second-line therapy remains uncertain. The purpose of this study is to explore the second-line mode of TC patients. MATERIALS AND METHODS: We evaluated the outcome of subjects with advanced TC between 2009 and 2023 in three medical centers, retrospectively. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). Kaplan-Meier was used for calculating Progression-free survival (PFS) and overall survival (OS). The factors affecting survival in the real world were evaluated by Cox analysis. RESULTS: Totally 136 patients were included in this study, the median PFS (mPFS) for all subjects was 5.97 months, and the median OS (mOS) was 25.03 months. According to patient's treatment modes, they are divided into monotherapy (n = 95) and combination therapy (n = 41), PFS manifested the difference between two groups (5.17 vs. 9.00 months, P = 0.043). OS also indicated a significant distinction (22.50 vs. 38.00 months, P = 0.017). Furthermore, there was a significant difference in PFS between patients using immunotherapy combined with chemotherapy and those with antivascular therapy (8.57 vs. 13.10 months, P = 0.047). CONCLUSION: In the second-line therapy for advanced TC, the efficacy of combination therapy was better than monotherapy, especially for immunotherapy combined with antivascular therapy.

[Sensitivity of colorectal cancer organoids to hyperthermic intraperitoneal chemotherapy with lobaplatin].

Objective: To investigate the sensitivity of tumor organoids derived from samples of colorectal cancer to lobaplatin and oxaliplatin hyperthermic perfusion in vitro and to assist clinical development of hyperthermic intraperitoneal chemotherapy. Method: Tumor samples and relevant clinical data were collected from patients with pathologically confirmed colorectal cancer in the Sixth Affiliated Hospital of Sun Yat-sen University from July 2021 to December 2022. Organoids were cultured and tumor tissue were passaged. In vitro hyperthermic perfusion experiments were performed on organoids with good viability. Firstly, 10 organoids were treated with oxaliplatin and lobaplatin at the following six concentrations: 1 000, 250, 62.5, 15.6, 3.9, and 0.98 µmol/L. The organoids were exposed to oxaliplatin at 42℃ for 30 minutes and to lobaplatin at 42℃ for 60 minutes. Dose-response curves of responses to in vitro hyperthermic perfusion with these two drugs were constructed and evaluated. Clinical doses of oxaliplatin and lobaplatin were further tested on 30 organoids. This testing revealed oxaliplatin was effective at 579 µmol/L at a hyperthermic perfusion temperature of 42℃ for 30 min and lobaplatin was effective at 240 µmol/L at a hyperthermic perfusion temperature of 42℃ for 60 minutes. Result: Thirty-two tumor organoids were cultured from samples of colorectal cancer. The median concentration required for oxaliplatin to eliminate 50% of tumor cells (IC50) was 577.45 µmol/L (IQR: 1846.09 µmol/L). The median IC50 for lobaplatin was 85.04 µmol/L (IQR: 305.01 µmol/L).The difference between the two groups was not statistically significant (Z=1.784, P=0.084). In seven of 10 organoids, lobaplatin showed a greater IC50 after in vitro hyperthermic perfusion than did oxaliplatin. Testing of 30 organoids with clinical doses of oxaliplatin and lobaplatin revealed that oxaliplatin achieved an average inhibition rate of 39.6% (95%CI: 32.1%‒47.0%), whereas the average rate of inhibition for lobaplatin was 89.7% (95%CI: 87.0%‒92.3%): this difference is statistically significant (t=‒15.282, P<0.001). Conclusion: The rate of inhibition achieved by hyperthermic perfusion of lobaplatin in vitro is better than that achieved by hyperthermic perfusion with oxaliplatin. Lobaplatin is more effective than oxaliplatin when administered by hyperthermic intraperitoneal perfusion and therefore has the potential to replace oxaliplatin in this setting.

[Explorations about the correlation between biological changes of meninges in periodontitis mice and cognitive impairment via single-cell RNA sequencing].

Objective: To clarify the potential correlation between biological changes of meninges in periodontitis mice and cognitive impairment by analyzing the biological changes of meninges in periodontitis mice using single-cell RNA sequencing. Methods: Thirty C57BL/6 mice were divided into two groups by using random number table method (15 mice in each group). Mice in the control group were locally administered 2% carboxyl methyl cellulose (CMC) without Porphyromonas gingivalis (Pg) on both buccal sides. A mixture of Pg W83 and 2% CMC was applied on both buccal sides in the experimental group mice three times a week, lasting for 16 weeks in total. The absorption of alveolar bone, locomotor activity and cognitive function, the activation of microglia and astrocytes in the cortex were observed and assessed. The mRNA expression levels of Occludin in meninges and brain were detected in two groups. Single-cell RNA sequencing data of meninges were processed by uniform manifold approximation and projection (UMAP). Differential genes expressions of endothelial cells were processed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In addition, real-time fluorescence quantitative PCR (RT-qPCR) was used to verify the expressions of transcription activating factor 3 (Atf3) and apolpoprotein L domain-containing 1 (Apold 1). Results: Methylene blue staining found the distances of buccal and palatal cement-enamel junction-alveolar bone crest in experimental mice [(185.60±17.60), (206.90±13.37) µm] increased significantly compared with the control group [(135.33±9.57), (163.05±14.98) µm] (t=5.02, P=0.002; t=4.37, P=0.005). Open field experiment showed the total distance and average speed of mice in the experimental group [(971.88±164.57) cm, (3.25±0.55) cm/s] were not statistically significant compared with the control group [(914.24±278.81) cm, (3.05±0.93) cm/s] (t=0.65, P=0.525; t=0.65, P=0.520). The recognition index of the experimental group [(48.02±16.92) %] was lower than the control group [(66.27±17.90) %] (t=2.40, P=0.027) by novel object recognition tests. Compared with the control group [(63.56±11.88) %], the alternation of experimental group [(50.99±14.17) %] was significantly decreased in Y maze tests (t=2.33, P=0.030). Immunohistochemistry results showed microglia and astrocytes were activated in the cortex of experimental mice. Compared with the control group (1.02±0.25, 1.04±0.31), the relative mRNA expressions of Occludin decreased significantly in the meninges and brain of periodontitis mice, respectively (0.61±0.10, 0.64±0.20) (t=3.47, P=0.010; t=2.66, P=0.024). By single-cell RNA sequencing, meninges cells were divided into 11 types, such as endothelial cells, fibroblasts, immune cells and so on. Endothelial cells were the main cell types in meninges [the control group: 26.47% (1 589/6 004), the experimental group: 26.26% (807/3 073)]. Compared with the control group [5.56% (334/6 004)], the percentage of granulocytes increased in the periodontitis mice [11.65% (358/3 073)]. Using clustering analysis to further focus on endothelial cells, GO enrichment analysis revealed differential genes were mainly related to angiogenesis, cell adhesion, apoptosis and so on. KEGG enrichment analysis revealed that differential genes were related to signaling pathways of interleukin-17, relaxin and so on. The relative mRNA expressions of Atf3 and Apold1 in meninges of periodontitis mice (0.42±0.24, 0.54±0.27) were significantly lower than the control group (1.03±0.26, 1.02±0.23) (t=3.88, P=0.005; t=3.02, P=0.017). Conclusions: The mice chronically infected with Pg W83 occurred memory impairment, neuroinflammation and changes of barrier function. In the meninges of periodontitis mice, there were infiltration of immune cells and down-regulation expressions of Atf3 and Apold1 by single-cell RNA sequencing. Meningeal immunity and changes of barrier function may play an important role in the cognitive impairment caused by periodontitis.

[Interpretation of specification for service of cancer screening for workers].

As the backbone force of China's social and economic construction, the health status of workers is closely related to the nation's productivity and social development. Currently, cancers have become one of the major diseases threatening the health of workers. However, there are still many shortcomings in the cancer screening services for the workers. To standardize cancer screening services for workers, ensure the quality of screening services, and improve the overall screening effectiveness, 19 institutions, including Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, have jointly formulated the Group Standard "Specification for service of cancer screening for workers (T/CHAA 023-2023)". This standard follows the principles of "legality, scientific rigor, advancement, and feasibility" and combines the frontier scientific advances in cancer screening. It clarifies the relevant requirements for service principles, service design, service delivery, service management, service evaluation, and improving worker cancer screening. Implementing this group standard will help connect the common screening needs of workers, employers, and cancer screening service providers, standardize the screening process, improve screening quality, and ultimately increase the early diagnosis rate and survival rate of cancer patients. Consequently, this group standard will help safeguard workers' health rights and interests, ensure the labor force resources, promote the comprehensive coordinated and sustainable development of society, and contribute to realizing the "Healthy China 2030" strategic policy.

[Gemcitabine long-term maintenance chemotherapy benefits patients with survival: a multicenter, real-world study of advanced breast cancer treatment in China].

Objective: This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients. Methods: Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy. Results: A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions: Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

[Use of the ETV6/RUNX1 probe to verify the performance of the fluorescence in situ hybridization probe before clinical detection].

Objective: To explore the standardized performance of a FISH probe before clinical detection. Methods: The probe sensitivity and specificity of ETV6/RUNX1 were analyzed via interphase and metaphase FISH in 20 discarded healthy bone marrow samples. The threshold system of the probe was established using an inverse beta distribution, and an interpretation standard was established. Finally, a parallel-controlled polymerase chain reaction detection study was conducted on 286 bone marrow samples from patients at our hospital. The clinical sensitivity, specificity, and diagnostic coincidence rate of ETV6/RUNX1 FISH detection were analyzed, and the diagnostic consistency of the two methods was analyzed by the kappa test. Results: The probe sensitivity and specificity of the ETV6/RUNX1 probe were 98.47% and 100%, respectively. When 50, 100, and 200 cells were counted, the typical positive signal pattern cutoffs were 5.81%, 2.95%, and 1.49%, respectively, and the atypical positive signal pattern cutoffs were 13.98%, 9.75%, and 6.26%, respectively. The clinical sensitivity of FISH was 96.1%, clinical specificity was 99.6%, diagnostic coincidence rate was 99.00%, diagnostic consistency test kappa value was 0.964, and P value was <0.001. Conclusion: For FISH probes without a national medical device registration certificate, standardized performance verification and methodology performance verification can be performed using laboratory developed test verification standards to ensure a reliable and accurate reference basis for clinical diagnosis and treatment.

Causal relationship between cigarette smoking behaviors and the risk of hernias: a Mendelian randomization study.

PURPOSE: As the global population continues to age, there is a noticeable yearly rise in the incidence of hernias. Simultaneously, smoking, a widespread addictive behavior and a significant contributor to mortality, has evolved into a pervasive public health concern. Existing literature has already established a connection between smoking and an increased risk of postoperative recurrence and postoperative infections following hernia surgery. However, there remains a dearth of research exploring the association between smoking and hernia morbidity. In this study, our objective is to systematically evaluate the causal relationship between cigarette smoking behaviors and hernia morbidity using a Mendelian randomization (MR) approach. METHODS: Hernia-related data were sourced from the FinnGen Biobank database, while cigarette smoking behavior data were gathered from the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. To assess the causal relationship, we employed five methods: the weighted median, the weighted mode the inverse variance weighted (IVW), MR-Egger, and the simple mode. Sensitivity analysis was conducted, incorporating Cochran's Q test, the MR-Egger intercept test, leave-one-out analysis, and funnel plot. The presentation of the causal relationship is expressed as an odds ratio (OR) along with their corresponding 95% confidence intervals (CI). RESULTS: Employing the IVW method as the reference standard, we found that smoking intensity is associated with an increased risk of diaphragmatic hernia (OR = 1.21, 95% CI 1.00-1.46, P = 0.047). These consistent findings were further corroborated by the weighted median and weighted mode methods (OR = 1.26, 95% CI 1.03-1.54, P = 0.026; OR = 1.25, 95% CI 1.02-1.52, P = 0.045). Conversely, when applying the IVW method, we identified no statistically significant causal relationship between smoking age, smoking initiation status, smoking cessation status, and the incidence of hernia. CONCLUSIONS: Our MR study has uncovered genetic evidence linking smoking intensity and the occurrence of diaphragmatic hernia. The risk of developing diaphragmatic hernia rises in tandem with the intensity of smoking. This emphasizes the crucial role of regularly advising patients to cease smoking in clinical settings.

[Study on reproductive toxicity of nano-cadmium sulfide with different particle sizes on male mice].

Objective: To investigate the reproductive toxicity of cadmium sulfide nanoparticles (Nano-CdS) with different particle sizes on male mice. Methods: In January 2019, 30 SPF grade male mice were randomly divided into a control group, an experimental group[CdS Ⅰ group (particle size approximately 5 nm), and a CdS Ⅱ group (particle size approximately 50 nm) ], with 10 mice in each group. The experimental group was orally gavaged with 100 mg/kg, once a day, while the control group was gavaged with an equal volume of physiological saline for 45 consecutive days. After 45 days, levels of cadmium accumulation in testis were determined directly by AAS, deformity and testicular histopathological changes were also observed. Serum testosterone levels were measured by enzyme-linked immunosorbentassay (ELISA), expression levels of P450scc, 17ß-HSD and P450c17 mRNA were determined by real-time PCR. P450c17 protein was determinated by Western Blot. Results: The histopathological results showed that the testes of the experimental group mice showed varying degrees of damage; Ultrastructural observation showed that the ultrastructure of mouse testicular cells in each experimental group showed varying degrees of mitochondrial expansion and disappearance of cristae, as well as irregular nuclear membranes. The degree of damage in CdS Ⅰ group was milder than that in CdS Ⅱ group. Compared with the control group, the cadmium content in the testes of the CdS Ⅰ and CdS Ⅱ groups significantly increased (P=0.001, 0.001), and the CdS Ⅱ group was higher than the CdS Ⅰ group (P=0.001). Compared with the control group, the levels of testosterone in the CdS Ⅰ and CdS Ⅱ groups decreased with statistical significance (P=0.001, 0.001). Real time fluorescence quantitative PCR results showed that compared with the control group, the experimental group's P450scc, 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly reduced, with statistically significant differences (P=0.001, 0.001, 0.001), and CdS Ⅱ group 17ß-HSD. The expression levels of 17ß-HSD and P450c17 mRNA were significantly lower than those of CdS Ⅰ group (P=0.001, 0.036). The Western Blot assay results showed that the expression levels of P450c17 protein in the testes of CdS Ⅰ and CdS Ⅱ groups of mice were significantly reduced, with statistical significance (P=0.001, 0.001) ; And the CdS Ⅱ group was significantly lower than the CdS Ⅰ group (P=0.001). According to Spearman correlation analysis, testosterone levels are correlated with P450scc, P450c17, 17ß-HSD mRNA. There is a highly positive correlation between 17ß-HSD mRNA levels, with statistically significant differences (r(s)=0.88, 0.80, 0.70, P=0.001, 0.001, 0.004) . Conclusion: Nano cadmium sulfide may induce reproductive toxicity by reducing the expression levels of key enzyme genes and enzyme protein activity in testosterone and its synthesis in mice, and the CdS Ⅱ group has a stronger toxic effect.

[Analysis of early diagnosis and prevention techniques for occupational pneumoconiosis based on patent perspectives in China's coal industry].

Occupational pneumoconiosis in the coal industry is an occupational disease that seriously endangers coal miners' health. Early diagnosis and prevention techniques are significant in controlling its incidence rate and reducing its harm. This article takes the patent data related to the early diagnosis and prevention of occupational pneumoconiosis in the coal industry, published from 1985 to 2021, as the research object. It uses tools such as the Derwent Data Analyzer (DDA) software, the Patyee Database, and the PatSnap Database to analyze the technological development trend and characteristics in this field from aspects of growth trend, primary patent holders, IPC classification layout, value, and research and development hotspots. The results show that the number of patent applications in this field indicates a rapid growth trend, mainly in the hands of Shandong Energy Group Co. Ltd., Shandong University of Science and Technology, China University of Mining and Technology, and other institutions or enterprises. Patent technology mainly involves spray dust reduction, dust removal fans, dust masks, and other aspects with high patent value and innovation ability. This article provides a new perspective and reference for preventing, diagnosing, and treating occupational pneumoconiosis in the coal industry.

[Evaluation of the clinical manifestations of COVID-19 in patients with aplastic anemia undergoing immunosuppressive therapy: a prospective cohort study (NICHE)].

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.

Over-activation of EFTUD2 correlates with tumor propagation and poor survival outcomes in hepatocellular carcinoma

PurposeElongation factor Tu GTP-binding domain containing 2 (EFTUD2) is an essential constituent of U5 small nuclear ribonucleoproteins (snRNPs) and plays a crucial role in spliceosome activation and cancer. The mechanism of EFTUD2 on carcinogenesis and development of liver cancer still need further study.MethodsBioinformatic analysis was performed to find differential expressed genes and related pathways. Western blotting and quantitative PCR assays were used to verify the EFTUD2 expression in HCC cell lines and tumor tissues of liver cancer patients. Transfection of shRNAs in SKHEP1 and Huh7 cell lines was conducted to explore the mechanisms of EFTUD2 in HCC. CCK-8 method, colony formation, and cell cycle detection kit were used to detect the proliferation. A tumor model in nude mice was used to explore the role of EFTUD2 in liver cancer in vivo.ResultsBased on the tumor tissues and para-tumor tissues in our HCC patients, we identified EFTUD2 as highly expressed in HCC tissues (P < 0.001). Bioinformatic analysis from the TCGA database also supported this biological phenomenon (P = 1.911e−17). Furtherly, the results of clinical specimens and TCGA data suggested that higher EFTUD2 expression levels correlated with high histologic grades, high pathological grades, and poor survival prognoses in HCC patients. And knockdown of EFTUD2 suppressed cell proliferation and colony formation in vitro. In vivo, knockdown of EFTUD2 constrained the tumor growing and expansion derived from SKHEP1 cells and induced a decrease in the tumor volume and tumor weight resected from nude mice. Furthermore, RNA sequencing based on EFTUD2 knockdown revealed that EFTUD2 affected target genes concerned with the cell cycle. Flow cytometric analyses in the SKHEP1 cell model revealed that knockdown significantly suppressed cell cycle course and caused cell cycle arrest in the G1 phase. CyclinD1 proteins were also inhibited by knocking down of EFTUD2.

Single-agent chemotherapy compared with combination chemotherapy as second-line treatment in extensive-stage small cell lung cancer: a retrospective analysis

OBJECTIVE: This retrospective analysis evaluates the clinical outcomes of extensive-stage small cell lung cancer (SCLC) patients who received second-line chemotherapy after platinum-based first-line chemotherapy, especially focusing on efficacy and toxicity between single-agent and combination chemotherapy. METHODS: We retrospectively reviewed 193 patients who received second-line chemotherapy for extensive-stage SCLC. Patients relapsing or progressing beyond 90 days were defined as sensitive recurrence patients, and below 90 days as refractory recurrence patients. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. RESULTS: 138 patients received combination chemotherapy and 55 received single-agent treatment. The objective response rate (ORR) was 25.4 % in the combination group and 9.1 % in the single-agent group (p = 0.012). The disease control rate (DCR) was 65.2 and 34.5 %, respectively, (p < 0.001). The progression-free survival (PFS) was 3.80 months in the combination group and 2.13 months in the single-agent group (p = 0.001). In the sensitive recurrence group, the median PFS was 3.80 months in combination group and 3.23 months in single-agent group (p = 0.092). In the refractory recurrence group, the median PFS was 2.83 and 1.30 months, respectively (p = 0.001). The grade III/IV toxicity in single-agent group is much lower than the combination group (56.4 vs. 74.6 %, p = 0.013). CONCLUSION: Our retrospective data suggest a potential role of prolonging the PFS for combination treatment in extensive-stage SCLC second-line treatment, especially for the refractory recurrence patients, but with more toxicity as compared to single-agent (AU)

Isolated oesophageal cyst connected with the bronchus

We report an unusual case of a patient with an oesophageal cyst connected to the bronchus. A 24-year old male with a two-year history of repeated attacks of chest infection and haemoptysis was found to have a cyst of 4 x 4 cm affecting the anterior and apical segments of the right upper lobe. The cyst was excised in its entirety and the histopathological study of the cyst showed stratified squamous epithelium with submucosal and muscular layer but no cartilage. The pathological diagnosis was an oesophageal cyst. No previous case of isolated oesophageal cyst connected to the bronchus has been reported according to the available literature.