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Abstract Background It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. Methods A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. Results The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063–7.342) and HPV33 (OR = 4.361; 95% CI 2.307–8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579–3.787), HPV51 (OR = 1.651; 95% CI 1.086–2.510) and HPV58(OR = 1.661; 95% CI 1.166–2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101–3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329–4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127–2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. Conclusion HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Abstract Background There is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC. Methods Seventy-two stage III or IV NSCLC patients who received chemoimmunotherapy were enrolled in this study. IVIM and DKI were performed before treatment. The patients were classified as responders group and non-responders group according to the Response Evaluation Criteria in Solid Tumors 1.1. The histogram parameters of ADC, Dslow, Dfast, f, Dk and K were measured using whole tumor volume ROI and single slice ROI analysis methods. Variables with statistical differences would be included in stepwise logistic regression analysis to determine independent parameters, by which the combined model was also established. And the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of histogram parameters and the combined model. Results ADC, Dslow, Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P

ObjectiveThis retrospective cohort study aimed to investigate the composition and diversity of lung microbiota in patients with severe pneumonia and explore its association with short-term prognosis.MethodsA total of 301 patients diagnosed with severe pneumonia underwent bronchoalveolar lavage fluid metagenomic next-generation sequencing (mNGS) testing from February 2022 to January 2024. After applying exclusion criteria, 236 patients were included in the study. Baseline demographic and clinical characteristics were compared between survival and non-survival groups. Microbial composition and diversity were analyzed using alpha and beta diversity metrics. Additionally, LEfSe analysis and machine learning methods were employed to identify key pathogenic microorganism associated with short-term mortality. Microbial interaction modes were assessed through network co-occurrence analysis.ResultsThe overall 28-day mortality rate was 37.7% in severe pneumonia. Non-survival patients had a higher prevalence of hypertension and exhibited higher APACHE II and SOFA scores, higher procalcitonin (PCT), and shorter hospitalization duration. Microbial α and β diversity analysis showed no significant differences between the two groups. However, distinct species diversity patterns were observed, with the non-survival group showing a higher abundance of Acinetobacter baumannii, Klebsiella pneumoniae, and Enterococcus faecium, while the survival group had a higher prevalence of Corynebacterium striatum and Enterobacter. LEfSe analysis identified 29 distinct terms, with 10 potential markers in the non-survival group, including Pseudomonas sp. and Enterococcus durans. Machine learning models selected 16 key pathogenic bacteria, such as Klebsiella pneumoniae, significantly contributing to predicting short-term mortality. Network co-occurrence analysis revealed greater complexity in the non-survival group compared to the survival group, with differences in central genera.ConclusionOur study highlights the potential significance of lung microbiota composition in predicting short-term prognosis in severe pneumonia patients. Differences in microbial diversity and composition, along with distinct microbial interaction modes, may contribute to variations in short-term outcomes. Further research is warranted to elucidate the clinical implications and underlying mechanisms of these findings.

PurposeThis two-center study aimed to explore the main prognostic factors affecting the final disease status in children and adolescents with differentiated thyroid cancer (caDTC) following total thyroidectomy and radioiodine therapy (RAIT).Materials and methodsAll caDTC patients from two centers in the period from 2004-2022 were retrospectively included. At the last follow-up, the patients’ disease status was assessed and classified as an incomplete response (IR) or as an excellent or indeterminate response (EIDR). Then, the difference in preablation stimulated thyroglobulin (ps-Tg) levels between the two groups was compared, and the threshold for predicting IR was determined using receiver operating characteristic (ROC) analysis. Moreover, univariate and multivariate analyses were conducted to identify the factors influencing the patients’ ultimate disease outcomes.ResultsA total of 143 patients (98 females, 45 males; median age 16 years) were recruited. After a median follow-up of 42.9 months, 80 patients (55.9%) exhibited an EIDR, whereas 63 patients (44.1%) exhibited an IR. Patients with an IR had significantly greater ps-Tg levels than did those with an EIDR (median ps-Tg 79.2 ng/mL vs. 9.3 ng/mL, p

ObjectivesNonselective beta blockers (NSBBs) or endoscopic therapies are currently recommended by guidelines for preventing the first variceal bleed in patients with high-risk varices. However, there is a lack of detailed treatment strategies for patients who are intolerant to both NSBBs and endoscopic approaches. Our study aimed to assess the efficacy and safety of variceal embolization as a primary prophylaxis method in cirrhosis patients who are not suitable candidates for NSBBs or endoscopic treatments.MethodsThe study included 43 cirrhotic patients with high-risk varices who were candidates for primary prophylaxis against variceal bleeding. These patients underwent variceal embolization at the Xijing Hospital between January 2020 and June 2022. The primary endpoint was the occurrence of bleeding from varices, and the secondary endpoints were the recurrence of varices and the emergence of complications.ResultsThe procedure of variceal embolization had a success rate of 93.0% (40 out of 43 patients). Over a 2-year follow-up period, the rate of variceal bleeding was 11.6% (5 out of 43 patients), the recurrence rate of varices was 14.0% (6 out of 43 patients), and the rate of severe complications was limited to 2.3% (1 out of 43 patients).ConclusionVariceal embolization is a viable primary prophylactic intervention for cirrhotic patients who are at risk of variceal bleeding when standard treatments, such as NSBBs or endoscopic therapies, are difficult to perform.

The concept of “enterotypes” in microbiome research has attracted substantial interest, particularly focusing on the abundance of Prevotella spp. in the human gut. In this study, the intricate dynamics of Prevotella spp. in the human gut microbiota was investigated, based on the metagenomic method. First, 239 fecal samples from individuals across four regions of China revealed a bimodal distribution, highlighting the abundance and variability in Prevotella spp. within the Chinese population. Second, the longitudinal cohort study included 184 fecal samples from 52 time points collected from seven individuals who demonstrated either the outbreaks or disappearances of Prevotella spp., emphasizing the transient nature of Prevotella abundance levels and suggesting shifts in Prevotella “enterotypes.” Furthermore, a turnover of the dominant Prevotella spp. was observed, indicating the potential presence of diverse subtypes of Prevotella enterotype. Notably, the genomic analysis demonstrated the persistence of specific Prevotella strains within individuals over extended periods, highlighting the enduring presence of Prevotella in the human gut. In conclusion, by integrating the temporal and geographical scales in our research, we gained deeper insights into the dynamics of Prevotella, emphasizing the importance of considering the dynamics at the time and species level in gut microbiota studies and their implications on human health.

Macrophages play an important role in peripheral nerve regeneration, but the specific mechanism of regeneration is still unclear. Our preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve regeneration. However, the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains unclear. This study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush injury. The functions of RAW 264.7 cells were elucidated by Cell Counting Kit-8 assay, flow cytometry, migration assays, phagocytosis assays, immunohistochemistry and enzyme-linked immunosorbent assay. Axonal debris phagocytosis was observed using the CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis) optical clearing technique during Wallerian degeneration. Macrophage inflammatory factor expression in different polarization states was detected using a protein chip. The results showed that neutrophil peptide 1 promoted the proliferation, migration and phagocytosis of macrophages, and CD206 expression on the surface of macrophages, indicating M2 polarization. The axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 intervention. Neutrophil peptide 1 also downregulated inflammatory factors interleukin-1α, -6, -12, and tumor necrosis factor-α in vivo and in vitro. Thus, the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration, which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

Myocardial fibroblasts play a crucial role in heart structure and function. In recent years, significant progress has been made in understanding the epigenetic regulation of myocardial fibroblasts, which is essential for cardiac development, homeostasis, and disease progression. In healthy hearts, cardiac fibroblasts (CFs) play a crucial role in synthesizing the extracellular matrix (ECM) when in a dormant state. However, under pathological and environmental stress, CFs transform into activated fibroblasts known as myofibroblasts. These myofibroblasts produce an excess of ECM, which promotes cardiac fibrosis. Although multiple molecular mechanisms are associated with CF activation and myocardial dysfunction, emerging evidence highlights the significant involvement of epigenetic regulation in this process. Epigenetics refers to the heritable changes in gene expression that occur without altering the DNA sequence. These mechanisms have emerged as key regulators of myocardial fibroblast function. This review focuses on recent advancements in the understanding of the role of epigenetic regulation and emphasizes the impact of epigenetic modifications on CF activation. Furthermore, we present perspectives and prospects for future research on epigenetic modifications and their implications for myocardial fibroblasts.

Background: Bone metastasis (BM) seriously affects the quality of life and reduces the survival time of patients with non-small-cell lung cancer (NSCLC). The genomic characteristics and potential targets of BMs are yet to be fully explored. Objective: To explore the genetic characteristics and potential targets of BM in NSCLC. Design: In all, 83 patients with NSCLC were retrospectively selected in this study. Genomic characterization of BMs was explored with the analysis of NGS results from primary tumors and BMs in 6 patients, then combined with NGS results of lung tumors in 16 patients with initial recurrence in bone to analyze mutations potentially associated with BMs, and finally, the correlation was further validated in 61 postoperative patients. Methods: The next generation sequencing (NGS) was performed to identify genomic differences between pulmonary primary tumors and BM. Fluorescence in situ hybridization and immunohistochemistry were performed in postoperative tumor tissues from patients who had undergone radical surgery to validate the predictive role of molecular targets for BM. The correlation between cyclin-dependent kinase 4 ( CDK4 ) and BM was evaluated by Pearson’s chi-square test. The university of alabama at birminghan cancer data analysis portal (UALCAN) was carried out for the detection of CDK4 expression in lung cancer and the relationship between CDK4 and clinicopathological parameters. The relationship between prognosis and CDK4 expression was analyzed by the Kaplan–Meier plotter. Results: The rate of gene amplification was increased (24% versus 36%) while gene substitution/indel was decreased (64% versus 52%) in BMs. The BM-specific mutations were analyzed in 16 recurrent patients which revealed the highest incidence of CDK4 amplification (18.8%). According to the Kaplan–Meier plotter database, the NSCLC patients with high CDK4 gene expression showed poor overall survival (OS) and recurrence-free survival (RFS) ( p

Abstract Background Gastric cardia adenocarcinoma (GCA) is classified as Siewert type II adenocarcinoma at the esophagogastric junction in Western countries. The majority of GCA patients do not exhibit early warning symptoms, leading to over 90% of diagnoses at an advanced stage, resulting in a grim prognosis, with less than a 20% 5‐year survival rate. Method Metabolic features of 276 GCA and 588 healthy controls were characterized through a widely‐targeted metabolomics by UPLC‐MS/MS analysis. This study encompasses a joint pathway analysis utilizing identified metabolites, survival analysis in both early and advanced stages, as well as high and negative and low expression of HER2 immunohistochemistry staining. Machine learning techniques and Cox regression models were employed to construct a diagnostic panel. Results A total of 25 differential metabolites were consistently identified in both discovery and validation sets based on criteria of p

Objective: This study aimed to investigate the underlying reasons for unexplained elevated thyroglobulin (Tg) in postoperative papillary thyroid cancer (PTC) patients according to follow-up results post RAT and to explore the long-term clinical outcomes and prognostic factors associated with these patients. Methods: From April 2016 to June 2019, a retrospective study was conducted on postoperative PTC patients who underwent RAT at our institution. Patients with preablative stimulated thyroglobulin (psTg) > 10 ng/mL but no structurally evident disease were enrolled. The causal categorization for elevated Tg was analyzed 6 months post RAT and the long-term therapeutic responses were assessed at the end of follow-up. To identify risk factors influencing recurrence-free survival (RFS), both univariate and multivariate Cox regression analysis were employed. Kaplan-Meier method was utilized for plotting survival curves. Results: A cohort of 165 subjects was enrolled for the analyses. Based on the results of a six-month follow-up, the postoperative unexplained elevated Tg among 165 patients could be ultimately attributed to thyroid remnant in 13.94% (23/165), biochemical disease in 60.00% (99/165), and structural disease in 26.06% (43/165). With a median follow-up of 58 months, 51 (30.91%), 34 (20.60%), 21 (12.73%), and 59 (35.76%) of the 165 patients achieved ER, IDR, BIR and SIR, respectively. Univariate analysis showed that N stage, TNM stage and suppressed Tg 6 months post RAT may be prognostic factors affecting RFS. Multivariate analysis showed that N1b stage [HR:2.749, P = 0.003] and II/III stage [HR:2.910, P = 0.001] were independent risk factors for RFS. Conclusion: The proportion of 165 postoperative PTC patients with unexplained elevated Tg developing structural disease within nearly 5 years was over 30%. Patients with N1b stage and higher TNM stage were more likely to develop structural disease.

ObjectivesTo accurately predict the risk of ischemic stroke, we established a radiomics model of carotid atherosclerotic plaque-based high-resolution vessel wall magnetic resonance imaging (HR-VWMRI) and combined it with clinical indicators.Materials and methodsIn total, 127 patients were finally enrolled and randomly divided into training and test cohorts. HR-VWMRI three-dimensional T1-weighted imaging (T1WI) and contrast-enhanced T1WI (T1CE) were collected. A traditional model was built by recording and calculating radiographic features of the carotid plaques and patients’ clinical indicators. After extracting radiomics features from T1WI and T1CE images, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select the optimal features and construct the radiomics_T1WI model and the radiomics_T1CE model. The traditional and radiomics features were used to build combined models. The performance of all the models predicting ischemic stroke was evaluated in the training and test cohorts, respectively.ResultsBody mass index (BMI) and intraplaque hemorrhage (IPH) were independently related to ischemic stroke and were used to build the traditional model, which achieved an area under the curve (AUC) of 0.79 versus 0.78 in the training and test cohorts, respectively. The AUC value of the radiomics_T1WI model is the lowest in the training and test cohorts, but the prediction performance is significantly improved when the model combines IPH and BMI. The AUC value of the combined_T1WI model was 0.78 and 0.81 in the training and test cohorts, respectively. In addition, in the training and test cohorts, the radiomics_T1CE model based on HR-VWMRI combined clinical characteristics, which is the combined_T1CE model, had the highest AUC value of 0.84 and 0.82, respectively.ConclusionCompared with other models, the radiomics_T1CE model based on HR-VWMRI combined clinical characteristics, which is a combined_T1CE model, can accurately predict the risk of ischemic stroke.

Abstract Background Silicosis is an important occupational disease caused by inhalation of free silica and is characterized by persistent pulmonary inflammation, subsequent fibrosis and lung dysfunction. Until now, there has been no effective treatment for the disease due to the complexity of pathogenesis. Fermented cordyceps powder (FCP) has a similar effect to natural cordyceps in tonifying the lung and kidney. It has started to be used in the adjuvant treatment of silicosis. This work aimed to verify the protective effects of FCP against silicosis, and to explore the related mechanism. Methods Wistar rats were randomly divided into four groups including the saline-instilled group, the silica-exposed group, the silica + FCP (300 mg/kg) group and the silica + FCP (600 mg/kg) group. Silicosis rat models were constructed by intratracheal instillation of silica (50 mg). Rats in the FCP intervention groups received the corresponding dose of FCP daily by intragastric gavage. Rats were sacrificed on days 7, 28 and 56 after treatment, then samples were collected for further analysis. Results FCP intervention reduced the infiltration of inflammatory cells and the concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) at days 7, 28, 56, and decreased the expression of collagen, α-smooth muscle actin (α-SMA) and fibronectin (FN) at days 28 and 56 in the lung of silicosis rats. FCP also decreased the immune response of Th1 and Th17 at days 7, 28, 56 and inhibited the enhancement of the Th2 response at day 56. Conclusions FCP intervention could alleviate silica-induced pulmonary inflammation and fibrosis, the protective effect may be achieved by reducing Th1 and Th17 immune responses and inhibiting the enhancement of the Th2 response.

Abstract Background The aim of this study was to determine the prevalence of high-risk human papillomavirus (HR-HPV) and the correlation between multiple infections and cervical lesions. Methods The current study involved population-based sample of 20,059 women who underwent cervical screening for 15 HR-HPV genotypes with ThinPrep cytologic test (TCT) results. The correlation between multiple HPV genotype infections and cervical lesions was also determined. The odds ratios (ORs) were calculated to assess co-infection patterns for each genotype with 15 other genotypes and the additive statistical interactions were evaluated. Results There was a bimodal pattern among multiple HPV infections, with a peak in the younger group and a second peak in the elderly group. Indeed, most multiple HPV genotypes exhibited a bimodal pattern. The most common HPV type in patients with high-grade squamous intraepithelial lesions (HSILs) was HPV-16, followed by HPV-52, HPV-58, and HPV-33. The most frequent HPV type in patients with cervical cancer was HPV-16, followed by HPV-58 and HPV-33. Women with multiple infections were at a increased risk of low-grade squamous intraepithelial lesions [LSIL] (OR = 2.01; 95% CI 1.38–2.93) and HSIL (OR 2.28; 95% CI 1.36–3.81) when compared to women with single infections. patients with cervical cancer had the higher percentage of multiple HPV infections. Based on the data herein, we suggest that HPV-33 and HPV-58 may also be high-risk HPV types worthy of increased surveillance and follow-up. Conclusion: Our findings suggested that the association between multiple HPV infections and HSIL and LSIL are stronger compared to single HPV infections. There may be some specific combinations that synergistically affected the risk of HSIL and LSIL.

With the continuous development of science and technology, laser ranging technology will become more efficient, convenient, and widespread, and it has been widely used in the fields of medicine, engineering, video games, and three-dimensional imaging. A time-of-flight (ToF) camera is a three-dimensional stereo imaging device with the advantages of small size, small measurement error, and strong anti-interference ability. However, compared to traditional sensors, ToF cameras typically exhibit lower resolution and signal-to-noise ratio due to inevitable noise from multipath interference and mixed pixels during usage. Additionally, in environments with scattering media, the information about objects gets scattered multiple times, making it challenging for ToF cameras to obtain effective object information. To address these issues, we propose a solution that combines ToF cameras with single-pixel imaging theory. Leveraging intensity information acquired by ToF cameras, we apply various reconstruction algorithms to reconstruct the object’s image. Under undersampling conditions, our reconstruction approach yields higher peak signal-to-noise ratio compared to the raw camera image, significantly improving the quality of the target object’s image. Furthermore, when ToF cameras fail in environments with scattering media, our proposed approach successfully reconstructs the object’s image when the camera is imaging through the scattering medium. This experimental demonstration effectively reduces the noise and direct ambient light generated by the ToF camera itself, while opening up the potential application of ToF cameras in challenging environments, such as scattering media or underwater.

Peripheral nerve injury (PNI) is a complex and protracted process, and existing therapeutic approaches struggle to achieve effective nerve regeneration. Recent studies have shown that mesenchymal stem cells (MSCs) may be a pivotal choice for treating peripheral nerve injury. MSCs possess robust paracrine capabilities, and exosomes, as the primary secretome of MSCs, are considered crucial regulatory mediators involved in peripheral nerve regeneration. Exosomes, as nanocarriers, can transport various endogenous or exogenous bioactive substances to recipient cells, thereby promoting vascular and axonal regeneration while suppressing inflammation and pain. In this review, we summarize the mechanistic roles of exosomes derived from MSCs in peripheral nerve regeneration, discuss the engineering strategies for MSC-derived exosomes to improve therapeutic potential, and explore the combined effects of MSC-derived exosomes with biomaterials (nerve conduits, hydrogels) in peripheral nerve regeneration.

Abstract Aim To evaluate role function and job satisfaction, determine their relationship, and explore the factors influencing job satisfaction among community nurses in China. Design Cross‐sectional study. Methods This study was conducted between March and June 2020 on a cluster random sampling of 302 community nurses from 24 community health centres and stations in Xi'an, China. Self‐reported data were collected using the Demographics Questionnaire, Role Function of Community Nurses Questionnaire, and Job Satisfaction of Community Nurses Scale. Descriptive statistics, Pearson's correlation analysis, and multiple linear regression analyses were performed to analyse data. Results Community nurses' main role function was organiser and manager (M = 2.56, SD = 0.987) and coordinator (M = 2.43, SD = 0.971). The lowest job satisfaction was for salary and benefits (M = 3.12, SD = 0.891) and personal development (M = 3.65, SD = 0.738). A positive correlation was found between the roles of caregiver, educator, navigator, and salary and benefits (p

Abstract Background Some clinicians used levothyroxine (LT4) treatment for mild subclinical hypothyroidism (SCH) pregnant women (2.5

Abstract Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described smoking-related malignancy. The pathogenesis of SMARCA4-UT is the mutational inactivation and loss of expression of a subunit encoding the mammalian switch/sucrose nonfermenting ATPase-dependent chromatin remodeling complex (which can be mobilized using adenosine triphosphate hydrolysis nucleosomes and regulate other cellular processes including development, differentiation, proliferation, and apoptosis), in particular SMARCA4 and SMARCA2. The dynamic activity of this complex plays an important role in regulating the activation and repression of gene expression programs. SMARCA4-UT exhibits morphological features similar to the malignant rhabdoid tumor (MRT), small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT), and INI1-deficient tumor, but SMARCA4-UT differs from SCCOHT and MRT from a genomic perspective. SMARCA4-UT mainly involves the mediastinum and lung parenchyma, and appears as a large infiltrative mass that easily compresses surrounding tissues. At present, chemotherapy is a common treatment, but its efficacy is not clear. Moreover, the inhibitor of the enhancer of zeste homolog 2 showed promising efficacy in some patients with SMARCA4-UT. This study aimed to review the clinical characteristics, diagnosis, treatment, and prognosis of SMARCA4-UT.

ObjectiveWe aimed to explore the predictive value of stimulated thyroglobulin (sTg) and pre-ablation antithyroglobulin (pa-TgAb) products for the effect of radioiodine therapy (RAIT) on TgAb-positive differentiated thyroid cancer (DTC) patients.MethodsIn this study, we enrolled 265 patients with TgAb-positive DTC who underwent RAIT after total thyroidectomy (TT). Based on the last follow-up result, the patients were divided into two groups: the excellent response (ER) group and the non-excellent response (NER) group. We analyzed the factors related to the effect of RAIT.ResultsThe ER group consisted of 197 patients. The NER group consisted of 68 patients. For the univariate analysis, we found that the maximal tumor diameter, whether with extrathyroidal extension (ETE), bilateral or unilateral primary lesion, multifocality, preoperative TgAb (preop-TgAb), pa-TgAb, sTg × pa-TgAb, initial RAIT dose, N stage, and surgical extent (modified radical neck dissection or not), showed significant differences between the ER group and NER group (all p-values 100 mCi (50.50 months vs. 38.00 months, p = 0.030).ConclusionWe found the sTg and pa-TgAb conducts is a good predictor of the efficacy of RAIT in TgAb-positive DTC patients. It can play a very positive and important role in optimizing treatment, improving prognosis, and reducing the burden of patients.

The United Nations Secretary-General Mechanism (UNSGM) for investigation of the alleged use of chemical and biological weapons is the only established international mechanism of this type under the UN. The UNGSM may launch an international investigation, relying on a roster of expert consultants, qualified experts, and analytical laboratories nominated by the member states. Under the framework of the UNSGM, we organized an external quality assurance exercise for nominated laboratories, named the Disease X Test, to improve the ability to discover and identify new pathogens that may cause possible epidemics and to determine their animal origin. The “what-if” scenario was to identify the etiological agent responsible for an outbreak that has tested negative for many known pathogens, including viruses and bacteria. Three microbes were added to the samples, Dabie bandavirus, Mammarenavirus, and Gemella spp., of which the last two have not been taxonomically named or published. The animal samples were from Rattus norvegicus, Marmota himalayana, New Zealand white rabbit, and the tick Haemaphysalis longicornis. Of the 11 international laboratories that participated in this activity, six accurately identified pathogen X as a new Mammarenavirus, and five correctly identified the animal origin as R. norvegicus. These results showed that many laboratories under the UNSGM have the capacity and ability to identify a new virus during a possible international investigation of a suspected biological event. The technical details are discussed in this report.

A study for human gut microbiota composition in 7 healthy Chinese adult subjects across several years provides a valuable perspective on the dynamics of microbiota composition over time.

Abstract Background Identifying polymorphism clades on phylogenetic trees could help detect punctual mutations that are associated with viral functions. With visualization tools coloring the tree, it is easy to visually find clades where most sequences have the same polymorphism state. However, with the fast accumulation of viral sequences, a computational tool to automate this process is urgently needed. Results Here, by implementing a branch-and-bound-like search method, we developed an R package named sitePath to identify polymorphism clades automatically. Based on the identified polymorphism clades, fixed and parallel mutations could be inferred. Furthermore, sitePath also integrated visualization tools to generate figures of the calculated results. In an example with the influenza A virus H3N2 dataset, the detected fixed mutations coincide with antigenic shift mutations. The highly specificity and sensitivity of sitePath in finding fixed mutations were achieved for a range of parameters and different phylogenetic tree inference software. Conclusions The result suggests that sitePath can identify polymorphism clades per site. The clustering of sequences on a phylogenetic tree can be used to infer fixed and parallel mutations. High-quality figures of the calculated results could also be generated by sitePath.

Electrochemical hydrogen-participating processes are commonly relevant in multiple clean energy technologies. Here, authors achieve in situ quantification of H sorption kinetics during Pd-catalyzed CO2 reduction, unravelling its key role within the interfacial network of local pH, proton donors and CO2 molecules.

Heart Failure (HF) is a complex clinical syndrome in which the heart is unable to provide enough blood flow to meet metabolic needs and lacks efficient venous return. HF is a major risk factor for morbidity and mortality with cardiovascular diseases globally. Despite enormous research, the molecular markers relevant to disease prognosis and management remain not well understood. Here, we analyzed the whole transcriptomes of 18 failing hearts and 15 non-failing hearts (predominantly of Caucasian origin), by applying the standard in silico tools. The analyses revealed novel gene-markers including ALKBH5 of mRNA demethylation and KMT2E of histone modification processes, significantly over-expressed in the HF compared with the non-failing hearts (FDR

Accurately identifying immune cell types in single-cell RNA-sequencing (scRNA-Seq) data is critical to uncovering immune responses in health or disease conditions. However, the high heterogeneity and sparsity of scRNA-Seq data, as well as the similarity in gene expression among immune cell types, poses a great challenge for accurate identification of immune cell types in scRNA-Seq data. Here, we developed a tool named sc-ImmuCC for hierarchical annotation of immune cell types from scRNA-Seq data, based on the optimized gene sets and ssGSEA algorithm. sc-ImmuCC simulates the natural differentiation of immune cells, and the hierarchical annotation includes three layers, which can annotate nine major immune cell types and 29 cell subtypes. The test results showed its stable performance and strong consistency among different tissue datasets with average accuracy of 71-90%. In addition, the optimized gene sets and hierarchical annotation strategy could be applied to other methods to improve their annotation accuracy and the spectrum of annotated cell types and subtypes. We also applied sc-ImmuCC to a dataset composed of COVID-19, influenza, and healthy donors, and found that the proportion of monocytes in patients with COVID-19 and influenza was significantly higher than that in healthy people. The easy-to-use sc-ImmuCC tool provides a good way to comprehensively annotate immune cell types from scRNA-Seq data, and will also help study the immune mechanism underlying physiological and pathological conditions.

Abstract Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2 years (range 45–72). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6/7) and relatively low objective response rate (ORR) (42/9%, 3/7). The median progression free survival (mPFS) for this treatment reached 2 months (1–6 months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q/V mutation of EGFR exon 18.

Objective To evaluate the application effect of Q-TRUST clinical communication training course in the training recruits of emergency department. Methods The experimental group was selected from new staff of the emergency department at Peking Union Medical College Hospital from October 2019 to September 2021.Totally 120 recruits from October 2017 to September 2019 were selected as the control group with 60 in each. The control group was adopted traditional centralized training, and the experimental group was adopted Q-TRUST clinical communication training. The basic information of the students in the two groups was collected, and the communication theory assessment was conducted after the training. The results of patient satisfaction and dispute complaints in the depart-ment within 2 years after the training were collected. The training effect evaluation of experimental group was obtained through questionnaire survey. Results There was no significant difference in age and education background between the two groups. The communication theory assessment score of the experimental group was 84.10±5.27, significantly higher than the control group (72.23±4.48)(P＜0.05). In the experimental group, the score of medical satisfaction after Q-TRUST training was 97.29±1.52, and the number of medical complaints was 15.In the control group. the score of medical satisfaction was 90.75±1.56 and 24 cases of medical complaints were obtained after traditional training. The experimental group was significantly better than the control group(P＜0.05). In the experimental group,the average score of the overall training effect of was 9.43±0.59, the degree of conformity with demand was 9.35±0.80.The results showed that the students in the experimental group were more satisfied with Q-TRUST training course and had high demand evaluation. How to quickly establish trust was 9.72±0.45; how to tell bad news 9.58±0.50; how to improve the efficiency of conversation 9.55±0.22; early identification of high-risk communication patients 9.47±0.87. In the feedback of experimental group, 100% of trainees believed that their communication skills was improved, 93.3% of dispute resolution ability was improved, 90% of communication efficiency and trust building were improved, 86.7% of identification for high-risk patients were improved and 83.3% of etiquette was improved. Conclusions Q-TRUST clinical communication training course can quickly improve the communication ability of new staff, enhance confidence, and better adapt to clinical works of emergency department.

Abstract Background This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. Methods A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan–Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. Results There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P

Uterine lymphoma is rare and usually occurs in middle-aged women. The clinical symptoms lack any specific characteristics. Imaging characteristics usually include uterine enlargement with density and uniform signal soft tissue masses. Magnetic resonance T2 weighted imaging, enhanced scanning, diffusion weighted imaging and apparent diffusion coefficient values have certain characteristics. The gold standard for diagnosis remains a pathological examination of a biopsy specimen. The special feature of this current case was that the uterine lymphoma occurred in an 83-year-old female patient that presented with a pelvic mass for more than 1 month. Based on the imaging findings, a primary uterine lymphoma was considered, but her advanced age of onset did not match the disease. After pathological confirmation, the patient was diagnosed with uterine lymphoma and she received eight cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) plus local radiotherapy for the large masses. The patients achieved good results. Follow-up enhanced computed tomography imaging showed that the uterine volume had significantly reduced compared with before treatment. The diagnosis of elderly patients with uterine lymphoma can provide a more accurate plan for subsequent treatment.

Background: Realgar, a traditional mineral medicine containing arsenic, has been utilized for a long time in Asian nations like China and India. Realgar is primarily excreted in proto-form, and its active components are believed to be the soluble portion. The biological events involved in absorption, transportation, metabolism, and excretion are poorly understood. Objective: In this review, we attempt to systematically elaborate the in vivo process of realgar from absorption to excretion and investigate its possible mechanism, so that people can gain a better understanding of the chemical substance basis of realgar and serve as a reference for realgar efficacy, toxicity research, and clinical application. Methods: The relevant information and literature were extracted and retrieved from the National Library of Medicine (PubMed), Elsevier, the National Knowledge Infrastructure (CNKI), Wiley Analytical Science, Springer Link, the Web of Science, the Science Guide Chinese Pharmacopoeia, and other databases, using realgar, arsenic, absorption, transport, distribution, metabolism, excretion, intestinal flora, and anticancer as keywords. The process and possible mechanisms of realgar from absorption to excretion in vivo were summarized. Results: Realgar has a low bioavailability and only soluble arsenic is dissolved in the gastrointestinal tract. Arsenic is mostly absorbed by ion and molecular mimicry, transported to the bloodstream by carrier proteins, and distributed throughout the body's organs. The metabolism of arsenic in realgar includes reduction, oxidation, methylation, and mercaptan. Arsenic and its metabolites are mainly distributed in the blood and various organs, among which the blood is the highest level of arsenic distribution. Ultimately, the majority of arsenic and its metabolites are removed in the urine, whereas unabsorbed realgar is eliminated in the feces. Conclusion: The main ingredient of realgar (As4S4) is mainly found in its primary form in the gastrointestinal tract and excreted with feces in vivo, where it has little to no therapeutic effect. Realgar's efficacy and toxicity may be attributed to the soluble arsenic it contains, which includes inorganic arsenic such as AsIII and AsV as well as organic arsenic such as MMA and DMA, which are metabolites of inorganic arsenic. In vivo, soluble arsenic is absorbed, distributed, metabolized, accumulated, and excreted, and there is hepatoenteric circulation.

Abstract Background A majority (>70%) of Q fever patients in South Korea do not have a history of animal contact. Therefore, unconscious environmental exposure is suspected. The aim of this study was to investigate exposure of Q fever patients to environmental contamination and animal shedding. Methods Two goat farmers were enrolled. One was diagnosed with Q fever 3 years ago (Farm 1). Among 20 goats on Farm 1, five were tested randomly and found to be Q fever PCR‐positive. Three of the five were Q fever ELISA‐positive. Two of five environmental samples taken in 2015 were PCR‐positive. In 2018, 17 of 18 environmental samples were PCR‐positive. On Farm 2, 54 of the 77 goats were PCR‐positive, and 63 were ELISA‐positive. Twelve of 14 environmental samples were PCR‐positive. Repeat administration of oxytetracycline to goats led to a gradual reduction in PCR‐positive tests over a 5‐month period. However, PCR‐positivity of the farm environment persisted for 5 months. Conclusion The environment on farms owned by Q fever patients was contaminated extensively and persistently, even after antibiotic treatment of goats and environmental decontamination. Undetected environmental contamination can be a major source of sporadic Q fever infection in South Korea.

ABSTRACT: Objectives: We analysed the molecular features and antimicrobial susceptibility of Mycoplasma pneumoniae isolates from Weihai, China, in 2019. Methods: Pharyngeal swabs of 160 paediatric patients with pneumonia-related symptoms were collected and were subjected to culture and subsequent characteristic analysis. The characteristics of M. pneumoniae isolates were analysed by real-time PCR and genotyping. Antimicrobial susceptibility testing was performed against four antibiotics. All isolates were amplified for analysis of macrolide (ML) resistance mutations in domain V of the 23S rRNA gene and were genotyped using multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) and ‘AGT’ VNTR detection in the p1 gene. Results: The M. pneumoniae nucleic acid and culture-positive rate of 160 specimens were 88.1% (141/160) and 51.3% (82/160), respectively. Almost all isolates were ML-resistant (81/82). Point mutation at position 2063 in 23S rRNA was identified in all ML-resistant isolates. The ML resistance rate of M. pneumoniae genotype 2 isolates was 97.6% (41/42). MLVA types 4/5/7/2 and 4/5/7/3 belonged to genotype 1, while type 3/5/6/2 belonged to genotype 2. The numbers of ‘AGT’ VNTR in the p1 gene from all isolates was in the range of 5–15. Conclusion: This is the first report that the two genotypes of M. pneumoniae were present in a relatively equivalent ratio, with genotype 2 slightly predominant, in paediatric patients in Weihai in 2019, and the overall ML resistance rate was close to 100%. The minimum inhibitory concentration (MIC) of erythromycin in M. pneumoniae with ML resistance mutation A2063T in Weihai was higher than previously reported.

Background and purpose: The co‐occurrence of amyloid‐β pathology in Parkinson's disease (PD) is common; however, the role of amyloid‐β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD. Methods: Ninety‐six patients with PD who underwent 18F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan. Results: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa‐induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group. Conclusions: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD. [ABSTRACT FROM AUTHOR]

Abstract The choices of the treatments for femoral neck fractures (FNF) remain controversial. The purpose of this study is to evaluate the prognoses of the variable pitch fully threaded headless cannulated screws (HCS) in the fixation of femoral neck fractures and to compare them with those of partially threaded cannulated screws (PCS). Between 1st January 2012 and 31st December 2016, there were 89 patients with the main diagnose of FNF who accepted the treatment of closed reduction cannulated screw fixation in Peking University People’s Hospital. 34 cases of PCS and 23 cases of HCS met the criterion. The characteristics, prognoses and the imaging changes of all cases were described and the differences between the two groups were compared. Statistical analyses were performed using SPSS version 23.0 (SPSS Inc., USA). Mann–Whitney U test, Analysis of Variance and Chi-square test were used. Statistical significance was defined as P value (two sided) less than 0.05. There was no significant difference in the general characteristics, fracture classifications and reduction quality between the two groups. HCS group had a significant lower angle decrease rate (30.4% vs. 58.8%, P = 0.035), femoral neck shortening rate (26.1% vs. 52.9%, P = 0.044) and screw back-sliding rate (21.7% vs. 50.0%, P = 0.032), but a higher screw cut-out rate (21.7% vs. 0.0%, P = 0.008). In non-displacement fracture subgroup, HCS had significant higher Harris Score (92 vs. 90, P = 0.048). Compared with PCS, HCS had a lower screw back-sliding rate, femoral shortening rate, angle decrease rate and similar function score, but would result in more screw cut-outs in displaced FNF. As a conclusion, HCS should not be used in displaced FNF due to its higher screw cut-out rate, and its potential advantage in non-displaced FNF needs to be further proved. Further qualified investigations with a larger scale of patients and longer follow-up are needed in the future.

Co-infection of RNA viruses may contribute to their recombination and cause severe clinical symptoms. However, the tracking and identification of SARS-CoV-2 co-infection persist as challenges. Due to the lack of methods for detecting co-infected samples in a large amount of deep sequencing data, the lineage composition, spatial–temporal distribution, and frequency of SARS-CoV-2 co-infection events in the population remains unclear. Here, we propose a hypergeometric distribution–based method named Cov2Coinfect with the ability to decode the lineage composition from 50,809 deep sequencing data. By resolving the mutational patterns in each sample, Cov2Coinfect can precisely determine the co-infected SARS-CoV-2 variants from deep sequencing data. Results from two independent and parallel projects in the United States achieved a similar co-infection rate of 0.3–0.5 % in SARS-CoV-2 positive samples. Notably, all co-infected variants were highly consistent with the co-circulating SARS-CoV-2 lineages in the regional epidemiology, demonstrating that the co-circulation of different variants is an essential prerequisite for co-infection. Overall, our study not only provides a robust method to identify the co-infected SARS-CoV-2 variants from sequencing samples, but also highlights the urgent need to pay more attention to co-infected patients for better disease prevention and control.