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Abstract Background The question of whether segmentectomy and lobectomy have similar survival outcomes for patients with early-stage non-small cell lung cancer (NSCLC) is a matter of debate. Methods A cohort study and randomized controlled trial were included, comparing segmentectomy and lobectomy, by utilizing computerized access to the Pubmed, Web of Science, and Cochrane Library databases up until July 2022. The Cochrane Collaboration tool was used to evaluate the randomized controlled trials, while the Newcastle-Ottawa Scale (NOS) was used to evaluate the cohort studies. Sensitivity analyses were also carried out. Results The analysis incorporated 17 literature studies, including one randomized controlled trial and 16 cohort studies, and was divided into a segmentectomy group (n = 2081) and a lobectomy group (n = 2395) based on the type of surgery the patient underwent. Each study was followed up from 27 months to 130.8 months after surgery. Over survival (OS): HR = 1.14, 95%CI(0.97,1.32), P = 0.10; disease-free survival (DFS): HR = 1.13, 95%CI(0.91,1.41), P = 0.27; recurrence-free survival (RFS): HR = 0.95, 95%CI(0.81,1.12), P = 0.54. Conclusion The results of the study suggest that the survival outcomes of the segmentectomy group were not inferior to that of the lobectomy group. Segmentectomy should therefore be considered as a treatment option for early stage NSCLC.

Abstract Background It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. Main body Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1β (IL-1β) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. Conclusion Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

Abstract Due to the continuous progress of constructing sustainable environments in China, the role played by the Chinese central government as the main body for promoting green development is worth studying. Because China’s ecological civilization building has been steadily progressing. Governments at all levels in China have prioritised the development of environmental civilization as a key aspect of regional growth. However, the actual impact and mechanisms of influence of this construction still require further investigation. This paper constructs a government environmental attention index using word frequency found in the Report on the Work of the Government. It uses a long difference model to study the impact and mechanism of government environmental attention on urban green efficiency, carbon emissions and air quality. The results show that the government’s ecological attention can improve green efficiency, and air quality, but it can also lead to increased carbon emissions, and the impact is particularly evident in the eastern and western regions of the country. This is because the government’s emphasis on the environment significantly impacts on environmental regulations and technological progress, and is directly influenced by fiscal bias and financial pressure. Given the results, we put forward some policy suggestions that local governments should improve the intensity of local environmental regulation, encourage green technology innovation, provide encouraging conditions for environmental development, and establish a long-term strategic vision. The findings in this study has implications for promoting the implementation of local governments’ environmental protection and the development of sustainable societies in China.

BackgroundEchinococcus granulosus is a widespread zoonotic parasitic disease, significantly impacting human health and livestock development; however, no vaccine is currently available for humans. Our preliminary studies indicate that recombinant antigen P29 (rEg.P29) is a promising candidate for vaccine.MethodsSheep were immunized with rEg.P29, and venous blood was collected at various time points. Serum was isolated, and the presence of specific antibodies was detected using ELISA. We designed and synthesized a total of 45 B cell monopeptides covering rEg.P29 using the overlap method. ELISA was employed to assess the serum antibodies of the immunized sheep for recognition of these overlapping peptides, leading to the preliminary identification of B cell epitopes. Utilizing these identified epitopes, new single peptides were designed, synthesized, and used to optimize and confirm B-cell epitopes.ResultsrEg.P29 effectively induces a sustained antibody response in sheep, particularly characterized by high and stable levels of IgG. Eight B-cell epitopes of were identified, which were mainly distributed in three regions of rEg.P29. Finally, three B cell epitopes were identified and optimized: rEg.P2971-90, rEg.P29151-175, and rEg.P29211-235. These optimized epitopes were well recognized by antibodies in sheep and mice, and the efficacy of these three epitopes significantly increased when they were linked in tandem.ConclusionThree B-cell epitopes were identified and optimized, and the efficacy of these epitopes was significantly enhanced by tandem connection, which indicated the feasibility of tandem peptide vaccine research. This laid a solid foundation for the development of epitope peptide vaccine for Echinococcus granulosus.

Abstract Moxibustion has been shown to have a potential antihypertensive effect, but its applicability for the primary care of hypertension is unclear. The authors conducted a multicenter randomized controlled trial (RCT) with patient preference arms to investigate the effect, safety, cost‐effectiveness, and compliance of moxibustion in community patients with hypertension. Patients with primary hypertension were enrolled from seven communities randomly or nonrandomly assigned to receive self‐administered moxibustion + the original hypertensive regimen or the original hypertensive regimen alone for 6 months. The authors mainly evaluated the effects of moxibustion on hypertensive outcomes and adverse events. As a result, a total of 160 and 240 patients were recruited into the randomized and nonrandomized arms, respectively, with 87.5% completing the follow‐up. At month 6, there was a significantly greater reduction in systolic blood pressure (SBP) (difference: −10.57 mmHg), a higher proportion of responders (82.2% vs. 53.7%; odds ratio 4.00), and better improvements in hypertensive symptoms and quality of life (QoL) in the moxibustion group than in the control group in the randomized population, but there was no significant between‐group difference in diastolic blood pressure (DBP). The nonrandomized findings showed the same effect direction for all outcomes, except for DBP. All moxibustion‐related adverse events were mild. In conclusion, moxibustion can reduce SBP and improve hypertensive symptoms and QoL in community patients with hypertension, with good safety and low cost, although its effect on DBP remains uncertain. The findings suggest that moxibustion may be an appropriate technique for community primary care of hypertension.

Abstract Background To comprehensively elucidate the genomic and mutational features of lung cancer cases, and lung adenocarcinoma (LUAD), it is imperative to conduct ongoing investigations into the genomic landscape. In this study, we aim to analyze the somatic mutation profile and assessed the significance of these informative genes utilizing a retrospective LUAD cohort. Methods A total of 247 Chinese samples were analyzed to exhibit the tumor somatic genomic alterations in patients with LUAD. The Cox regression analysis was employed to identify prognosis‐related genes and establish a predictive model for stratifying patients with LUAD. Results In the Dianjiang People's Hospital (DPH) cohort, the top five frequent mutated genes were (Epidermal growth factor receptor) EGFR (68%), TP53 (30%), RBM10 (13%), LRP1B (9%), and KRAS (9%). Of which, EGFR is a mostly altered driver gene, and most mutation sites are located in tyrosine kinase regions. Oncogene pathway alteration and mutation signature analysis demonstrated the RTK‐RAS pathway alteration, and smoking was the main carcinogenic factor of the DPH cohort. Furthermore, we identified 34 driver genes in the DPH cohort, including EGFR (68%), TP53 (30.4%), RBM10 (12.6%), KRAS (8.5%), LRP1B (8.5%), and so on, and 45 Clinical Characteristic‐Related Genes (CCRGs) were found to closely related to the clinical high‐risk factors. We developed a Multiple Parameter Gene Mutation (MPGM) risk model by integrating critical genes and oncogenic pathway alterations in LUAD patients from the DPH cohort. Based on publicly available LUAD datasets, we identified five genes, including BRCA2, Anaplastic lymphoma kinase (ALK), BRAF, EGFR, and Platelet‐Derived Growth Factor Receptor Alpha (PDGFRA), according to the multivariable Cox regression analysis. The MPGM‐low group showed significantly better overall survival (OS) compared to the MPGM‐high group (p

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to progressive joint damage. Circular RNA (circRNA) can regulate the inflammatory response of fibroblast-like synoviocytes (FLSs) in RA, influencing the disease progression. Paeoniflorin (PF) is the main active ingredient extracted from Paeonia lactiflora and is known for its anti-inflammatory effect. This study aims to explore the potential mechanisms by which hsa_circ_009012 and PF regulate the inflammatory response in RA. Methods: RNA expression of hsa_circ_009012, has-microRNA-1286 (miR-1286), toll-like receptor 4 (TLR4), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was assessed by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting (WB). Cell inflammation markers (TNF-α, IL-1β, IL-6) were assessed by RT-qPCR and immunofluorescence (IF). Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to test cell viability, cell cycle distribution, and migration. Results: Hsa_circ_009012 was highly expressed in RA-FLS. Hsa_circ_009012 over-expression facilitated the inflammation in RA-FLS and was closely associated with the miR-1286/TLR4 axis. Paeoniflorin inhibited inflammation and the expression of hsa_circ_009012 and TLR4, while upregulating the expression of miR-1286 in RA-FLS. Moreover, the upregulation of hsa_circ_009012 reversed the repressive effect of paeoniflorin on RA-FLS progression. Conclusion: Paeoniflorin inhibits the inflammation of RA-FLS via mediating the hsa_circ_009012/miR-1286/TLR4/NLRP3 axis.

Ovarian serous carcinoma (OSC) has high mortality, making accurate prognostic evaluation vital for treatment selection. This study develops a three-year OSC survival prediction model using machine learning, integrating pathological image features with clinical data. First, a Convolutional Neural Network (CNN) was used to classify the unlabeled pathological images and determine whether they are OSC. Then, we proposed a multi-scale CNN combined with transformer model to extract features directly. The pathological image features were selected by Elastic-Net and then combined with clinical information. Survival prediction is performed using Support Vector Machine (SVM), Random Forest (RF), and XGBoost through cross-validation. For comparison, we segmented the tumor area as the region of interest (ROI) by U-net and used the same methods for survival prediction. The results indicated that (1) the CNN-based cancer classification yielded satisfactory results; (2) in survival prediction, the RF model demonstrated the best performance, followed by SVC, and XGBoost was less effective; (3) the segmented tumor ROIs are more accurate than those predicted directly from the original pathology images; and (4) predictions combining pathological images with clinical information were superior to those solely based on pathological image features. This research provides a foundation for the diagnosis of OSC and individualized treatment, affirming that both ROI extraction and clinical information inclusion enhance the accuracy of predictions.

BackgroundThe HIV infection status among men who have sex with men (MSM) in China is a cause for concern. Post-exposure prophylaxis (PEP) serves as a highly effective biomedical preventive measure against HIV infection. Substantial evidence has established an association between PEP utilization and risk behaviors among MSM, but whether the utilization of PEP has an impact on risk behaviors remains unknown. This study sought to elucidate the impact of PEP usage on risk behaviors among MSM and provide recommendations for developing targeted HIV prevention programs.MethodsA cohort study was conducted in Qingdao, China, from April 2021 to January 2022. Participants were enlisted by volunteers from community-based organizations through a snowball sampling method. Face-to-face interviews were conducted to collect sociodemographic and behavioral information of participants. The study encompassed a retrospective investigation, baseline survey, and follow-up survey, representing periods before, during, and after PEP usage, respectively. Generalized estimating equations, fitting a Poisson regression model, were applied to scrutinize changes in risk behaviors of MSM during and after PEP usage, in comparison to before PEP usage.ResultsA total of 341 MSM were recruited in the cohort study, with 179 individuals completing the follow-up survey. In comparison to before PEP usage, there was a significant increase in the proportion of Rush Popper usage (17.6% vs. 23.8% vs. 29.6%) and commercial sexual partners (10.9% vs. 17.6% vs. 21.8%) among MSM during and after PEP usage. Before PEP usage, 88.7% of MSM reported having ≥3 temporary sexual partners in the last 6 months. This proportion exhibited no significant change during PEP usage (91.8%), but it significantly increased to 97.8% after PEP usage (P < 0.05). Notably, there was a significant decrease in group sex during and after PEP usage compared to before PEP usage (30.8% vs. 21.4% vs. 21.2%).ConclusionThe utilization of PEP may impact risk behaviors among MSM, potentially leading to increased Rush Popper usage, temporary sexual partners, and commercial sexual partners after PEP usage, accompanied by a decrease in group sex. Further research is imperative to elucidate the impact of PEP utilization on MSM and develop targeted HIV prevention programs.

We analyzed a large amount of published petrological, mineralogical, and geochemical data from the Niutitang, Wufeng-Longmaxi, Dawuba, Liangshan, and Longtan organic-rich shales. These include marine shales and marine-continental transitional shales. The main marine organic-rich shales include the Niutitang, Wufeng-Longmaxi, and Dawuba shales, while the main marine-continental organic-rich transitional shales include the Liangshan and Longtan shales. The marine organic-rich shales were generally deposited under anoxic conditions, and are generally brittle siliceous-rich lithofacies, which is a type I organic-matter dominated. In contrast to the marine organic-rich shales, the marine-continental transitional organic-rich shales were most likely deposited under dysoxic to oxic conditions. They are generally less brittle argillaceous-rich lithofacies, that are type III organic-matter dominated. Of the five organic-rich shales, the Niutitang and Wufeng-Longmaxi organic-rich shales are over-mature shales, and the Dawuba, Liangshan, and Longtan organic-rich shales are high-maturity to over-mature shales. The spots with siliceous rock floor on the western edge of the Xuefeng uplift is a favorable area for future exploration of shale gas in the Niutitang organic-rich shale. The Chishui terrestrial basin and center of the aulacogen are the faverable areaa for shale gas expolation and development of the Wufeng-Longmaxi and Dawuba organic-rich shales, respectively. More basic geological research work is needed to select favorable areas for the Liangshan and Longtan organic-rich shales. To accurately guide future shale gas exploration and development, more research is needed on the relationship between the sedimentary environment, the lithofacies, and the reservoir properties of the shales.

Detecting deep-sea megabenthic organisms is of foremost importance for seabed resource surveys, typical habitat protection, and biodiversity surveys. However, the complexity of the deep-sea environment, uneven illumination, and small biological targets that are easily obscured all increase target detection difficulty significantly. To address these, this paper proposes a deep-sea megabenthic detection algorithm, DS-YOLO, based on YOLOv5s. To improve the detection ability of the model for deep-sea megabenthic organisms, the space-to-depth module and the spatial pyramid pooling cross stage partial channel module are introduced in the Backbone layer to enlarge the receptive field and enhance the retention of small-scale features. Then, the space-to-depth and normalization-based attention modules and the Add and Concat functions of the bidirectional feature pyramid network are introduced in the Neck layer to increase the multiscale fusion ability of the model and highlight the insignificant features. Finally, the two branches of the decoupling header output the category and location of the target, which causes the model to utilize the feature information to the maximum extent. Experiments showed that DS-YOLO improved mAP0.5 from 89.6% to 92.4% and mAP0.5:0.95 from 65.7% to 72.3% compared to the original YOLOv5s on the homemade dataset and outperformed other algorithms in the YOLO series. DS-YOLO reaches 84.7 FPS for deployment on mobile platforms. In addition, the combined DS-YOLO and DeepSORT algorithm can be used to calculate the abundance and community structure of deep-sea megabenthos. The model outperforms general target detection models for deep-sea megabenthos detection and is suitable for use in complex deep-sea environments.

BackgroundMen who have sex with men (MSM) have a high prevalence of HIV and a low rate of HIV testing in China. HIV self-testing (HIVST) presents a viable strategy for expanding HIV testing among MSM. However, the impact of HIVST on risk behaviors among MSM remains controversial. Our study sought to ascertain this impact.MethodsFrom April 2021 to January 2022, a mixed-methods study was conducted in Qingdao City, employing both quantitative and qualitative methodologies. The quantitative component entailed a cohort study among MSM who had used HIVST. Generalized estimating equations fitting Poisson regressions were used to analyze the changes in risk behaviors of MSM in short time after HIVST (ST-HIVST) and longer time after HIVST (LT-HIVST) compared to before HIVST. Subsequently, we conducted in-depth interviews with 18 MSM who completed the follow-up to delve deeper into the impact of HIVST on MSM.ResultsA total of 410 MSM were recruited in the cohort, of whom 83 were lost to follow-up. Compared to before HIVST, there were no significant changes in risk behaviors in ST-HIVST (p > 0.05), while the proportion of recreational drugs abuse (20.7% vs. 33.3%), commercial sex (14.6% vs. 22.9%), and unprotected anal sex (95.9% vs. 98.5%) increased significantly in LT-HIVST (p

Echinococcosis is a common human and animal parasitic disease that seriously endangers human health and animal husbandry. Although studies have been conducted on vaccines for echinococcosis, to date, there is no human vaccine available for use. One of the main reasons for this is the lack of in-depth research on basic immunization with vaccines. Our previous results confirmed that recombinant antigen P29 (rEg.P29) induced more than 90% immune protection in both mice and sheep, but data on its induction of sheep-associated cellular immune responses are lacking. In this study, we investigated the changes in CD4+ T cells, CD8+ T cells, and antigen-specific cytokines IFN-γ, IL-4, and IL-17A after rEg.P29 immunization using enzyme-linked immunospot assay (ELISPOT), enzyme-linked immunosorbent assay (ELISA), and flow cytometry to investigate the cellular immune response induced by rEg.P29 in sheep. It was found that rEg.P29 immunization did not affect the percentage of CD4+ and CD8+ T cells in peripheral blood mononuclear cells (PBMCs), and was able to stimulate the proliferation of CD4+ and CD8+ T cells after immunization in vitro. Importantly, the results of both ELISPOT and ELISA showed that rEg.P29 can induce the production of the specific cytokines IFN-γ and IL-17A, and flow cytometry verified that rEg.P29 can induce the expression of IFN-γ in CD4+ and CD8+ T cells and IL-17A in CD4+ T cells; however, no IL-4 expression was observed. These results indicate that rEg.P29 can induce Th1, Th17, and Tc1 cellular immune responses in sheep against echinococcosis infection, providing theoretical support for the translation of rEg.P29 vaccine applications.

Climate change which is mainly caused by carbon emissions is a global problem affecting the economic development and well-being of human society. Low-carbon agriculture is of particular significance in slowing down global warming and reaching the goal of “carbon peak and carbon neutrality”. Therefore, taking straw incorporation as an example, this paper aims to investigate the impact of risk preferences on farmers’ low-carbon agricultural technology (LCAT) adoption. Based on a two-phase micro-survey data of 1 038 rice farmers in Jiangsu, Jiangxi, and Hunan provinces, this paper uses experimental economics methods to measure farmers’ risk aversion and loss aversion to obtain the real risk preferences information of the farmers. We also explore the data to examine the actual LCAT adoption behavior of farmers. The results revealed that both risk aversion and loss aversion significantly inhibit farmers’ LCAT adoption: more risk-averse or more loss-averse farmers are less likely to adopt LCAT. It is further found that crop insurance, farm scale and governmental regulations can alleviate the negative impact of risk aversion and loss aversion on farmers’ LCAT adoption. Therefore, we propose that local governments need to promote low-carbon agricultural development by propagating the benefits of LCAT, extending crop insurance, promoting appropriate scale operations, and strengthening governmental regulations to promote farmers’ LCAT adoption.

Abstract Auditory neuropathy spectrum disorder (ANSD) is a hearing impairment caused by dysfunction of inner hair cells, ribbon synapses, spiral ganglion neurons and/or the auditory nerve itself. Approximately 1/7000 newborns have abnormal auditory nerve function, accounting for 10%-14% of cases of permanent hearing loss in children. Although we previously identified the AIFM1 c.1265 G > A variant to be associated with ANSD, the mechanism by which ANSD is associated with AIFM1 is poorly understood. We generated induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells (PBMCs) via nucleofection with episomal plasmids. The patient-specific iPSCs were edited via CRISPR/Cas9 technology to generate gene-corrected isogenic iPSCs. These iPSCs were further differentiated into neurons via neural stem cells (NSCs). The pathogenic mechanism was explored in these neurons. In patient cells (PBMCs, iPSCs, and neurons), the AIFM1 c.1265 G > A variant caused a novel splicing variant (c.1267-1305del), resulting in AIF p.R422Q and p.423-435del proteins, which impaired AIF dimerization. Such impaired AIF dimerization then weakened the interaction between AIF and coiled-coil-helix-coiled-coil-helix domain-containing protein 4 (CHCHD4). On the one hand, the mitochondrial import of ETC complex subunits was inhibited, subsequently leading to an increased ADP/ATP ratio and elevated ROS levels. On the other hand, MICU1-MICU2 heterodimerization was impaired, leading to mCa2+ overload. Calpain was activated by mCa2+ and subsequently cleaved AIF for its translocation into the nucleus, ultimately resulting in caspase-independent apoptosis. Interestingly, correction of the AIFM1 variant significantly restored the structure and function of AIF, further improving the physiological state of patient-specific iPSC-derived neurons. This study demonstrates that the AIFM1 variant is one of the molecular bases of ANSD. Mitochondrial dysfunction, especially mCa2+ overload, plays a prominent role in ANSD associated with AIFM1. Our findings help elucidate the mechanism of ANSD and may lead to the provision of novel therapies.

Marine shales from the Niutitang Formation and marine–continental transitional shales from the Longtan Formation are two sets of extremely important hydrocarbon source rocks in South China. In order to quantitatively compare the pore complexity characteristics between marine and marine–continental transitional shales, the shale and kerogen of the Niutitang Formation and the Longtan Formation are taken as our research subjects. Based on organic petrology, geochemistry, and low-temperature gas adsorption analyses, the fractal dimension of their pores is calculated by the Frenkel–Halsey–Hill (FHH) and Sierpinski models, and the influences of total organic carbon (TOC), vitrinite reflectance (Ro), and mineral composition on the pore fractals of the shale and kerogen are discussed. Our results show the following: (1) Marine shale predominantly has wedge-shaped and slit pores, while marine–continental transitional shale has inkpot-shaped and slit pores. (2) Cylindrical pores are common in organic matter of both shale types, with marine shale having a greater gas storage space (CRV) from organic matter pores, while marine–continental transitional shale relies more on inorganic pores, especially interlayer clay mineral pores, for gas storage due to their large specific surface area and high adsorption capacity (CRA). (3) The fractal characteristics of marine and marine–continental transitional shale pores are influenced differently. In marine shale, TOC positively correlates with fractal dimensions, while in marine–continental shale, Ro and clay minerals have a stronger influence. Ro is the primary factor affecting organic matter pore complexity. (4) Our two pore fractal models show that the complexity of the shale in the Longtan Formation surpasses that of the shale in the Niutitang Formation, and type I kerogen has more complex organic matter pores than type III, aiding in evaluating pore connectivity and flow effectiveness in shale reservoirs.

Mobile Industrial Internet of Things (IIoT) applications have achieved the explosive growth in recent years. The mobile IIoT has flourished and become the backbone of the industry, laying a solid foundation for the interconnection of all things. The variety of application scenarios has brought serious challenges to mobile IIoT networks, which face complex and changeable communication environments. Ensuring data secure transmission is critical for mobile IIoT networks. This paper investigates the data secure transmission performance prediction of mobile IIoT networks. To cut down computational complexity, we propose a data secure transmission scheme employing Transmit Antenna Selection (TAS). The novel secrecy performance expressions are first derived. Then, to realize real-time secrecy analysis, we design an improved Convolutional Neural Network (CNN) model, and propose an intelligent data secure transmission performance prediction algorithm. For mobile signals, the important features may be removed by the pooling layers. This will lead to negative effects on the secrecy performance prediction. A novel nine-layer improved CNN model is designed. Out of the input and output layers, it removes the pooling layer and contains six convolution layers. Elman, Back-Propagation (BP) and LeNet methods are employed to compare with the proposed algorithm. Through simulation analysis, good prediction accuracy is achieved by the CNN algorithm. The prediction accuracy obtains a 59% increase.

Objective To investigate the clinical significance of the inferior wall cartilage of the auditory meatus in surgical treatment of congenital first branchial cleft anomalies (CFBCAs) in children.Methods Twenty children diagnosed with CFBCAs who underwent surgery between December 2018 and June 2022 at our hospital were retrospectively analyzed and classified according to their Work lesion type. The guiding significance of the inferior wall cartilage in the surgical treatment of CFBCAs was summarized by investigating the adjacent relationships of the surgical lesions with the external auditory canal and facial nerve.Results Of the 20 patients, 16 were classified as Work type I and 4 as Work type II. The lesions were adjacent to the inferior wall cartilage of the auditory meatus in all children. Work type I lesions were located in the upper lateral aspect and were not adjacent to the facial nerve. Work type II lesions were located in the inferior-medial region of the facial nerve. The lesions were completely resected in all children. One patient experienced recurrence 3 months postoperatively because of a residual endochondral fistula. No patients developed facial paralysis or other complications.Conclusions The inferior wall cartilage of the auditory meatus may help to the identify the initial lesion of the CFBCAs and can be regarded as a guiding anatomical structure. These lesions can be completely resected. For resection of Work type II first branchial cleft lesions, the surgical incision can be narrower, and can be precisely positioned with the assistance of endoscope.

Pulmonary mucoepidermoid carcinoma (PMEC) is a rare tumor, particularly in children, and its clinical manifestations vary. When the tumor is small, it may be asymptomatic; however, with larger tumors, patients may present with symptoms such as recurring pneumonia, atelectasis, persistent cough, chest pain, and even hemoptysis. PMEC appears as an exophytic intrabronchial mass. This study aims to report on the clinical manifestations, imaging findings, treatment approaches, and prognosis of two children diagnosed with PMEC at our hospital between January 2018 and December 2022. The age of onset for both children was 9 years, and the masses were located in the right upper lobe bronchi. Following surgical treatment, both patients showed a good prognosis. In addition, we conducted a comprehensive review of the relevant literature to enhance the overall understanding of PMEC.

Osteomyelitis is a chronic inflammatory bone disease caused by infection of open fractures or post-operative implants. Particularly in patients with open fractures, the risk of osteomyelitis is greatly increased as the soft tissue damage and bacterial infection are often more severe. Staphylococcus aureus, one of the most common pathogens of osteomyelitis, disrupts the immune response through multiple mechanisms, such as biofilm formation, virulence factor secretion, and metabolic pattern alteration, which attenuates the effectiveness of antibiotics and surgical debridement toward osteomyelitis. In osteomyelitis, immune cells such as neutrophils, macrophages and T cells are activated in response to pathogenic bacteria invasion with excessive inflammatory factor secretion, immune checkpoint overexpression, and downregulation of immune pathway transcription factors, which enhances osteoclastogenesis and results in bone destruction. Therefore, the study of the mechanisms of abnormal immunity will be a new breakthrough in the treatment of osteomyelitis.

Abstract Background Metastasis of cancer causes more than 90% of cancer deaths and is severely damaging to human health. In recent years, several studies have linked sarcopenia to shorter survival in patients with metastatic cancer. Several predictive models exist to predict mortality in patients with metastatic cancer, but have reported limited accuracy. Methods We systematically searched Medline, EMBASE, and the Cochrane Library for articles published on or before October 14, 2022. Pooled Hazard Ratio (HR) estimates with 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was an increased risk of death or tumor progression in patients with metastatic cancer, which is expressed as progression-free survival (PFS). In addition, we performed subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. Results Sixteen retrospective cohort studies with 1,675 patients were included in the 888 papers screened. The results showed that sarcopenia was associated with lower progression-free survival (HR = 1.56, 95% CI = 1.19–2.03, I2 = 76.3%, P

Preeclampsia (PE) is a pregnancy-specific disorder attributed to deficient extravillous trophoblast (EVT) invasion into the uterus, but the mechanism of EVT invasion remains unclear. In this study, we found significantly elevated expression of microRNA 21 (miR21), which negatively regulates trophoblast invasion and migration, in preeclamptic placentae. Whole-genome RNA sequencing revealed that PPP2R2B, which encodes PP2A Bβ, and the Hippo pathway are downstream targets of miR21. The effects of miR21 on trophoblast mobility were abolished in LATS1T1079A/S909A and YAP-5SA mutants. Moreover, we found that PP2A Bβ dephosphorylates LATS1 via direct protein-protein interactions and thus modulates the phosphorylation and subcellular distribution of YAP. PPP2R2B overexpression ameliorated the miR21-induced LATS1-YAP phosphorylation and cytoplasmic sequestration of YAP, which resulted in the rescue of compromised trophoblast invasion and migration. The upregulation of placental miR21 abundance by placenta-specific nanoparticles loaded with agomir-miR21 during placentation interfered with PPP2R2B and activated the Hippo pathway in the placenta, leading to a PE-like phenotype. Thus, aberrant elevation of miR21 impairs EVT mobility by modulating the PP2A Bβ/Hippo axis, which is one of the causes of PE.

Rhenium is an extremely rare critical metal element in Earth’s continental crust. Owing to its extremely high melting point and heat-stable crystalline structure, rhenium is an essential component of alloy materials used in high-performance aircraft engines. Demand for rhenium resources is therefore growing. Currently, most rhenium is produced as a byproduct of molybdenum mining in porphyry copper–molybdenum deposits. Research has therefore focused on the enrichment characteristics of rhenium in this type of deposit, with little attention paid to rhenium in other types of deposits. This study reports the occurrence state and enrichment mechanism of rhenium in the Qianjiadian sandstone-type uranium deposit in the Songliao Basin, Northeast China. Sequential extraction revealed that the average proportions of different forms of rhenium are as follows: water-soluble (57.86%) > organic-sulfide-bound (13.11%) > residual (12.26%) > Fe/Mn oxide-bound (10.67%) > carbonate-bound (6.10%). Combining mineralogical analysis techniques such as SEM-EDS, EMPA, and XRD, it has been established that rhenium does not occur as a substitute in sulfides (e.g., molybdenite) or uranium minerals in various types of deposits. Instead, it is mainly adsorbed onto clay minerals and Fe-Ti oxides, and in a small number of other minerals (pyrite, organic matter, and pitchblende). Rhenium is similar to redox-sensitive elements such as uranium and vanadium, and it is transported in a water-soluble form by oxidizing groundwater to the redox transition zone for enrichment. However, unlike uranium, which generally forms as uranium minerals, rhenium is mainly adsorbed and enriched onto clay minerals (kaolinite and interlayered illite–smectite). Most of the rhenium in sandstone-type uranium deposits occurs in an ion-adsorption state, and is easily leached and extracted during in-situ leaching mining of uranium ores. This type of deposit demonstrates excellent production potential and will become a crucial recoverable resource for future rhenium supply.

Hypertrophic cardiomyopathy (HCM) is the most prominent cause of sudden cardiac death in young people. Due to heterogeneity in clinical manifestations, conventional HCM drugs have limitations for mitochondrial hypertrophic cardiomyopathy. Discovering more effective compounds would be of substantial benefit for further elucidating the pathogenic mechanisms of HCM and treating patients with this condition. We previously reported the MT-RNR2 variant associated with HCM that results in mitochondrial dysfunction. Here, we screened a mitochondria-associated compound library by quantifying the mitochondrial membrane potential of HCM cybrids and the survival rate of HCM-induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) in galactose media. 1-Deoxynojirimycin (DNJ) was identified to rescue mitochondrial function by targeting optic atrophy protein 1 (OPA1) to promote its oligomerization, leading to reconstruction of the mitochondrial cristae. DNJ treatment further recovered the physiological properties of HCM iPSC-CMs by improving Ca2+ homeostasis and electrophysiological properties. An angiotensin II-induced cardiac hypertrophy mouse model further verified the efficacy of DNJ in promoting cardiac mitochondrial function and alleviating cardiac hypertrophy in vivo. These results demonstrated that DNJ could be a potential mitochondrial rescue agent for mitochondrial hypertrophic cardiomyopathy. Our findings will help elucidate the mechanism of HCM and provide a potential therapeutic strategy.

Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production and function of these cytokines are usually dysregulated during malignant tumor progression. Considering their clinical potential and the early successful use of cytokines in cancer immunotherapy, such as interferon alpha-2b (IFNα-2b; IntronA®) and IL-2 (Proleukin®), cytokine-based therapeutics have been extensively evaluated in many follow-up clinical trials. Following these initial breakthroughs, however, clinical translation of these natural messenger molecules has been greatly limited owing to their high-degree pleiotropic features and complex biological properties in many cell types. These characteristics, coupled with poor pharmacokinetics (a short half-life), have hampered the delivery of cytokines via systemic administration, particularly because of severe dose-limiting toxicities. New engineering approaches have been developed to widen the therapeutic window, prolong pharmacokinetic effects, enhance tumor targeting and reduce adverse effects, thereby improving therapeutic efficacy. In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer. In addition, aiming to promote engineered cytokine-based cancer immunotherapy, we present a profound discussion about the feasibility of recently developed methods in clinical medicine translation.

Summary: Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children in resource-poor settings. To explore microbial influences on susceptibility, we screened 85 microbiota-associated metabolites for their effects on Cryptosporidium parvum growth in vitro. We identify eight inhibitory metabolites in three main classes: secondary bile salts/acids, a vitamin B6 precursor, and indoles. Growth restriction of C. parvum by indoles does not depend on the host aryl hydrocarbon receptor (AhR) pathway. Instead, treatment impairs host mitochondrial function and reduces total cellular ATP, as well as directly reducing the membrane potential in the parasite mitosome, a degenerate mitochondria. Oral administration of indoles, or reconstitution of the gut microbiota with indole-producing bacteria, delays life cycle progression of the parasite in vitro and reduces the severity of C. parvum infection in mice. Collectively, these findings indicate that microbiota metabolites impair mitochondrial function and contribute to colonization resistance to Cryptosporidium infection.

Management of ulcerative colitis can require a combination of treatments targeting different pathways. Here the authors design a therapy for ulcerative colitis based on a multitargeted genetic circuit to simultaneously target TNF-α, B7-1 and integrin α4, and show the therapy is effective in male mice with induced or spontaneous genetic colitis.

Worst pattern of invasion (WPOI) is a parameter used to quantify tumor invasiveness of oral squamous cell carcinoma (OSCC). Here the authors show that a fibroblast subset characterized by the expression of the oxytocin receptor is enriched in highly invasive WPOI 4-5 OSCC tumors and can be targeted to reduce the desmoplastic stroma and tumor metastasis.

Abstract Background Cushing’s disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD. Case presentation A girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively. Conclusions We reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

Background & aimsLittle is known about molecular biomarkers that predict the response and prognosis in unresectable hepatocellular carcinoma (HCC) treated with programmed death (PD)-1 inhibitors.MethodsA total of 62 HCC patients who underwent next-generation sequencing were retrospectively included in our department for this study. Patients with unresectable disease were subjected to systemic therapy. PD-1 inhibitors intervention (PD-1Ab) group and nonPD-1Ab group included 20 and 13 patients, respectively. Primary resistance was defined as initial on-treatment progression or progression with an initial stable disease of less than 6 months.ResultsChromosome 11q13 amplification (Amp11q13) was the most common copy number variation in our cohort. Fifteen (24.2%) patients harbored Amp11q13 in our dataset. Patients with Amp11q13 showed higher level of Des-γ-carboxy-prothrombin (DCP), tumor number and were more prone to be combined with portal vein tumor thrombosis (PVTT). In the PD-1Ab group, the proportion of progressive disease (PD) in patients with Amp11q13 was significantly higher than that in patients with nonAmp11q13 (100% vs 33.3%, P=0.03). In the nonPD-1Ab group, the proportion of PD in patients with Amp11q13 and nonAmp11q13 had no significant difference (0% vs 11.1%, P>0.99). In the PD-1Ab group, the median progression-free survival (PFS) was 1.5 months in Amp11q13 patients vs 16.2 months in non-Amp11q13 patients (HR, 0.05; 95% CI 0.01-0.45; P = 0.0003). No significant difference was observed in the nonPD-1Ab group. Notably, we found that hyperprogressive disease (HPD) might be associated with Amp11q13. The increased density of Foxp3+ Treg cells in HCC patients with Amp11q13 might be one of potential mechanisms.ConclusionHCC patients with Amp11q13 are less likely to benefit from PD-1 blockade therapies. These findings may help guide the use of immunotherapy for HCC in routine clinical practice.

BackgroundTotal pancreatectomy (TP) has been increasingly performed in recent years. However, studies on diabetes management after TP during different postoperative periods are still limited.ObjectivesThis study aimed to evaluate the glycemic control and insulin therapy of patients undergoing TP during the perioperative and long-term follow-up period.MethodsNinety-three patients undergoing TP for diffuse pancreatic tumors from a single center in China were included. Based on preoperative glycemic status, patients were divided into three groups: nondiabetic group (NDG, n = 41), short-duration diabetic group (SDG, preoperative diabetes duration ≤12 months, n = 22), and long-duration diabetic group (LDG, preoperative diabetes duration >12 months, n = 30). Perioperative and long-term follow-up data, including the survival rate, glycemic control, and insulin regimens, were evaluated. Comparative analysis with complete insulin-deficient type 1 diabetes mellitus (T1DM) was conducted.ResultsDuring hospitalization after TP, glucose values within the target (4.4-10.0 mmol/L) accounted for 43.3% of the total data, and 45.2% of the patients experienced hypoglycemic events. Patients received continuous intravenous insulin infusion during parenteral nutrition at a daily insulin dose of 1.20 ± 0.47 units/kg/day. In the long-term follow-up period, glycosylated hemoglobin A1c levels of 7.43 ± 0.76% in patients following TP, as well as time in range and coefficient of variation assessed by continuous glucose monitoring, were similar to those in patients with T1DM. However, patients after TP had lower daily insulin dose (0.49 ± 0.19 vs 0.65 ± 0.19 units/kg/day, P < 0.001) and basal insulin percentage (39.4 ± 16.5 vs 43.9 ± 9.9%, P = 0.035) than patients with T1DM, so did those using insulin pump therapy. Whether in the perioperative or long-term follow-up period, daily insulin dose was significantly higher in LDG patients than in NDG and SDG patients.ConclusionsInsulin dose in patients undergoing TP varied according to different postoperative periods. During long-term follow-up, glycemic control and variability following TP were comparable to complete insulin-deficient T1DM but with fewer insulin needs. Preoperative glycemic status should be evaluated as it could guide insulin therapy after TP.

Ultrafast extreme ultraviolet (XUV) transient absorption spectroscopy measures the time- and frequency-dependent light losses after light–matter interactions. In the linear region, the matter response to an XUV light field is usually determined by the complex refractive index [Formula: see text]. The absorption signal is directly related to the imaginary part of [Formula: see text], namely, the absorption index. The real part of [Formula: see text] refers to the real refractive index, which describes the chromatic dispersion of an optical material. However, the real refractive index information is usually not available in conventional absorption experiments. Here, we investigate the refractive index line shape in ultrafast XUV transient absorption spectroscopy by using a scheme that the XUV pulse traverses the target gas jet off-center. The jet has a density gradient in the direction perpendicular to the gas injection direction, which induces deflection on the XUV radiation. Our experimental and theoretical results show that the shape of the frequency-dependent XUV deflection spectra reproduces the refractive index line profile. A typical dispersive refractive index line shape is measured for a single-peak absorption; an additional shoulder structure appears for a doublet absorption. Moreover, the refractive index line shape is controlled by introducing a later-arrived near-infrared pulse to modify the phase of the XUV free induction decay, resulting in different XUV deflection spectra. The results promote our understanding of matter-induced absorption and deflection in ultrafast XUV spectroscopy.

Rib fracture is the most common injury in chest trauma. Most of patients with rib fractures were treated conservatively, but up to 50% of patients, especially those with combined injury such as flail chest, presented chronic pain or chest wall deformities, and more than 30% had long-term disabilities, unable to retain a full-time job. In the past two decades, surgery for rib fractures has achieving good outcomes. However, in clinic, there are still some problems including inconsistency in surgical indications and quality control in medical services. Before the year of 2018, there were 3 guidelines on the management of regional traumatic rib fractures were published at home and abroad, focusing on the guidance of the overall treatment decisions and plans; another clinical guideline about the surgical treatment of rib fractures lacks recent related progress in surgical treatment of rib fractures. The Chinese Society of Traumatology, Chinese Medical Association, and the Chinese College of Trauma Surgeons, Chinese Medical Doctor Association organized experts from cardiothoracic surgery, trauma surgery, acute care surgery, orthopedics and other disciplines to participate together, following the principle of evidence-based medicine and in line with the scientific nature and practicality, formulated the Chinese consensus for surgical treatment of traumatic rib fractures (STTRF 2021). This expert consensus put forward some clear, applicable, and graded recommendations from seven aspects: preoperative imaging evaluation, surgical indications, timing of surgery, surgical methods, rib fracture sites for surgical fixation, internal fixation method and material selection, treatment of combined injuries in rib fractures, in order to provide guidance and reference for surgical treatment of traumatic rib fractures.

Abstract Background Low- and middle-income countries have a high prevalence of primary hypertension, but its treatment and control are often low. Heat-sensitive moxibustion (HSM), an innovative acupoint stimulation technique, may be effective for treating hypertension and thus used appropriately in primary healthcare. The objective of this study is to investigate whether HSM is effective and safe for the treatment of primary hypertension in the community. Methods This study is a multicenter, pragmatic, randomized controlled trial (RCT) with patient-preference arms. Four hundred patients with primary hypertension from seven communities will be enrolled. Initially, the communities will be randomly assigned into two study clusters, one using compulsory randomization and the other allowing treatment selection by patient preferences. Then, patients in the compulsory randomization cluster will be randomized to receive HSM plus their original antihypertensive regimen (HSM group) or only their original antihypertensive regimen (control group) for 6 months. Patients in the patient preference cluster may choose to receive HSM or control if they have a preference; otherwise, patients will be randomly assigned. The primary outcome is the change in systolic blood pressure from baseline; secondary outcomes include change in diastolic blood pressure, dosage of antihypertensive drugs, quality of life (QoL), severity of hypertensive symptoms, and incidence of cardiovascular events. Patient compliance with the HSM regimen, the cost-effectiveness ratio, and safety outcomes will also be evaluated. Outcome data will be collected at 6 monthly visits. Discussion This trial will provide important evidence regarding HSM as a technique for primary hypertension in primary healthcare settings. Given the randomization with patient preferences considered, the trial will also allow analyzing patient-preference effects and the comparison of randomized and nonrandomized samples, to improve the robustness and extrapolation of study conclusions. Trial registration ClinicalTrials.gov NCT04788563 . Registered on March 9, 2021.

Abstract Microvascular invasion (MVI) is presently evaluated as a high-risk factor to be directly relative to postoperative prognosis of hepatocellular carcinoma (HCC). Up to now, diagnosis of MVI mainly depends on the postoperative pathological analyses with H&E staining assay, based on numbers and distribution characteristics of MVI to classify the risk levels of MVI. However, such pathological analyses lack the specificity to discriminate MVI in HCC specimens, especially in complicated pathological tissues. In addition, the efficiency to precisely define stages of MVI is not satisfied. Thus, any biomarker for both conforming diagnosis of MVI and staging its levels will efficiently and effectively promote the prediction of early postoperative recurrence and metastasis for HCC. Through bioinformatics analysis and clinical sample verification, we discovered that Stathmin 1 (STMN1) gene was significantly up-regulated at the locations of MVI. Combining STMN1 immunostaining with classic H&E staining assays, we established a new protocol for MVI pathological diagnosis. Next, we found that the degrees of MVI risk could be graded according to expression levels of STMN1 for prognosis prediction on recurrence rates and overall survival in early HCC patients. STMN1 affected epithelial-mesenchymal transformation (EMT) of HCC cells by regulating the dynamic balance of microtubules through signaling of “STMN1-Microtubule-EMT” axis. Inhibition of STMN1 expression in HCC cells reduced their lung metastatic ability in recipients of mouse model, suggesting that STMN1 also could be a potential therapeutic target for inhibiting HCC metastasis. Therefore, we conclude that STMN1 has potentials for clinical applications as a biomarker for both pathological diagnosis and prognostic prediction, as well as a therapeutic target for HCC.

Current treatments for toxoplasmosis are limited by adverse reactions and inability to cure chronic infections dominated by semi-dormant cyst forms. Here the authors demonstrate the potential of small molecule inhibitors of PheRS for controlling acute and chronic toxoplasmosis.

Abstract Background We aimed to investigate the clinical characteristics and islet β-cell function in patients with Klinefelter syndrome (KS) and hyperglycemia. Methods This is a retrospective study. In total, 22 patients diagnosed with KS were identified from the electronic medical record system, including 9 patients with hyperglycemia (total patients with hyperglycemia, THG-KS group) and 5 hyperglycemic KS patients with oral glucose tolerance test (OGTT) results (HG-KS group). An additional 5 subjects with hyperglycemia and 5 normal glucose tolerance (NGT) subjects matched based on body mass index were included as the HG group and NGT group, respectively. Data from clinical and laboratory examinations were collected. We further performed a literature review of KS and hyperglycemia. Results We found that KS patients developed abnormal glucose metabolism earlier in life than those without KS, and the median age was 17 years, ranging from 10 years to 19 years. Six of 17 (35.3%) patients were diagnosed with diabetes mellitus and 3 of 17 (17.6%) patients were diagnosed with prediabetes. Among 10 patients with both fasting blood glucose and insulin results recorded, there were 8 out of 17 (47.1%) KS patients had insulin resistance. The prevalence of hypertension and dyslipidemia was higher in patients with hyperglycemia and KS than in patients with NGT KS. Compared with the HG group, insulin sensitivity levels were lower in HG-KS group, whereas homeostasis model assessment of β-cell function levels (p = 0.047) were significantly, indicating higher insulin secretion levels in the HG-KS group. Conclusions KS patients develop hyperglycemia earlier in life than those without KS and show lower insulin sensitivity and higher insulin secretion. These patients also have a higher prevalence of other metabolic diseases and may have different frequencies of developing KS-related symptoms.

Ensuring food security in China is the primary task in solving the problems of ‘agriculture, countryside, and farmers’. Based on Chinese provincial panel data from 2009 to 2018, this paper evaluates the impact of a water rights trading pilot policy (WRTPP) on food security and examines its underlying mechanism. To overcome the estimation bias existing in previous studies, we use the difference-in-differences method, which can separate time effects from policy treatment effects and is an effective tool to compare the effect before and after policy implementation. We, therefore, use this method to evaluate the net effect of the WRTPP on food security. It is found that the WRTPP can help ensure food security. This effect reaches its maximum in the fourth year after the policy's implementation. It is further found that the WRTPP can improve the adoption of agricultural water-saving irrigation technology to increase the grain yield. Our conclusions complement existing evidence on the factors influencing food security. From the perspective of improving farmers’ water-saving irrigation technology, we confirm that the mechanism of the water rights trading pilot policy helps ensure food security. HIGHLIGHTS Water rights trading pilot policy can help guarantee food security.; The policy help guarantee food security by improving the adoption of water-saving irrigation technology.; This effect reaches its maximum in the fourth year after the implementation of the policy.; The policy will have a long-term effect on helping guaranteeing food security.; The research does not violate the parallel trend assumption of the difference-in-differences method.;

Introduction: Congenital piriform sinus fistula is a relatively rare type of disease in clinical practice, most occurring during childhood, but doctors have insufficient knowledge regarding this disease, easily misdiagnosing it. Objectives: This study aimed to identify the characteristics of deep neck abscess due to congenital piriform sinus fistula in children. Methods: We performed a retrospective study of 21 cases from January 2016 to August 2018 in our hospital. The onset age, clinical characteristics, auxiliary examination and clinical treatment of the patients was summarized to analyze the diagnosis, treatment characteristics and prognosis. Results: Children from 11 days to 12 years-old were enrolled, with an average age of 3.5 years. Twenty patients had left congenital piriform sinus fistula and 1 had right congenital piriform sinus fistula. Cervical enhanced computed tomography imaging showed gas-liquid equilibrium or air-shadow in the abscesses in 18 cases, and neck ultrasound demonstrated gas echo in the thyroid region in 10 cases. All patients underwent low temperature plasma to seal the internal fistula and returned to the hospital for electronic laryngoscope and neck ultrasound examination at 3 months, 6 months and 1 year after the surgery. No recurrence occurred in any patient. Conclusion: Congenital piriform sinus fistula is an important cause of deep neck abscess in children. The presence of purulent gas-liquid equilibrium or air shadow in cervical-enhanced computed tomography or ultrasound suggests a high possibility of the presence of an internal fistula, and endoscopic low temperature ablation can be done at the same time as the diagnostic endoscopy.

Background: Wild foxes play an important role in echinococcosis epidemics. There have been a few studies investigating Echinococcus spp. in the Qinghai-Tibet Plateau area, China, but none on the prevention and control of Echinococcus spp. in wild foxes. Methods: From 2016 March through December 2019, two wild fox dens were selected as two test sites based on prior long-term camera screening and observation. Anthelmintic praziquantel tablets were placed near the two dens of wild foxes, and the wild foxes freely consumed the anthelmintic drugs. Morphological methods were used to detect initially the parasite species, and PCR molecular methods were used to identify accurately parasite and host species. Results: Parasite eggs of E. multilocularis (2/11, 18.2%) were found in 11 fecal samples. Importantly, the eggs of E. multilocularis (1/21, 4.8%) were found again in the feces of the foxes one year later; moreover, the eggs of E. multilocularis (2/19, 10.5%) still existed in the feces of the foxes two years later. Conclusion: Wild foxes were repeatedly infected with E. multilocularis and that deworming for prevention and control is required at least twice per year. Prevention and control methods for echinococcosis in wild foxes were explored, providing a scientific basis for the prevention and control of echinococcosis in wild animals.

Infections of Echinococcus granulosus sensu stricto, E. multilocularis and E. shiquicus are usually prevalent or coendemic in wild canids in the Qinghai-Tibet Plateau area (QTPA) of China. Thus, an efficient method for the detection of infected hosts and the identification of Echinococcus species is needed. The present work aims to establish a multiplex PCR (mPCR) method that can simultaneously detect the three main Echinococcus species mentioned above, and provide technical support for the diagnosis, prevention and control of Echinococcus infection. Three pairs of specific primers were designed for this mPCR based on the Echinococcus mitochondrial genes in GenBank, and these primers were validated by specificity and sensitivity experiments and applied for simulated coinfection samples detection and filed samples. This mPCR method was able to successfully identify both simplex and mixed target Echinococcus spp. and generate expected amplicons of different sizes for each species. The sensitivity of this mPCR method was tested with serially diluted gene recombinant plasmid, and the results showed a detection threshold of less than 103 for both species. The specificity, which was assessed against 10 other parasites, was found to be 100%. The assay was also used on 15 simulated clinical samples, and the results confirmed the high reliability of the method, indicating that the mPCR method established in this study can be used to analyze clinical samples from the QTPA. This mPCR method has potential application in rapid detection, diagnosis and broad-scale screening and is expected to become a key technology for clinical detection and environmental monitoring.

Oral squamous cell carcinoma (OSCC) is the most common malignant tumor in the oral and maxillofacial regions, with a high rate of metastasis. Cancer-associated fibroblasts (CAFs) play critical roles in tumor growth, metastasis and invasion, making them attractive therapeutic targets for cancer treatment. As an old anti-coccidiosis drug for poultry, Halofuginone (HF) has also been reported to possess anti-fibrosis and anti-cancer activities in the recent decades. However, whether it works by targeting CAFs in OSCC, and the mechanisms involved remain unclear. In the present study, we observed HF dose-dependently inhibits OSCC-derived CAF viability and proliferation. Meanwhile, HF decreased the expressions of α-SMA, FSP-1 and PDGFRβ, markers of the malignant phenotype of CAFs, both at mRNA and protein levels. Furthermore, functional studies demonstrated that HF dramatically attenuates the promotion effect of CAFs on OSCC cell migration and invasion. Mechanistically, the inhibition of MMP2 secretion and the upstream TGF-β/Smad2/3 signaling pathway played an important role in these processes. In the orthotopic transplanted tongue carcinoma in mice model, we confirmed that HF administration inhibited tumor growth and lymph node metastasis (LNM) with reduced CAF population, MMP2 expression and collagen deposition in tumor. Altogether, these results indicate that HF can inhibit the migration and invasion of OSCC by targeting CAFs, which will provide new ideas for the treatment of OSCC.

The cestode Echinococcus multilocularis larva infection causes lethal zoonotic alveolar echinococcosis (AE), a disease posing a great threat to the public health worldwide. This persistent hepatic tumor-like disease in AE patients has been largely attributed to aberrant T cell responses, of which Th1 responses are impeded, whilst Th2 and regulatory T cell responses are elevated, creating an immune tolerogenic microenvironment in the liver. However, the immune tolerance mechanisms are not fully understood. Dendritic cells (DCs) are key cellular components in facilitating immune tolerance in chronic diseases, including AE. Here, we demonstrate that indoleamine 2,3-dioxygenase 1-deficient (IDO1-/-) mice display less severe AE as compared to wild-type (WT) mice during the infection. Mechanistically, IDO1 prevents optimal T cells responses by programming DCs into a tolerogenic state. Specifically, IDO1 prevents the maturation and migration potential of DCs, as shown by the significantly enhanced expression of the antigen-presenting molecule (MHC II), costimulatory molecules (CD80 and CD86), and chemokine receptors (CXCR4 and CCR7) in infected IDO1-/- mice as compared to infected wild-type mice. More importantly, the tolerogenic phenotype of DCs is partly reverted in IDO1-/- mice, as indicated by enhanced activation, proliferation, and differentiation of both CD4+ and CD8+ - T cells upon infection with Echinococcus multilocularis, in comparison with WT mice. Interestingly, in absence of IDO1, CD4+ T cells are prone to differentiate to effector memory cells (CD44+CD62L-); in contrast, CD8+ T cells are highly biased to the central memory phenotype (CD44+CD62L+). Overall, these data are the first to demonstrate the essential role of IDO1 signaling in inducing immunosuppression in mice infected with Echinococcus multilocularis.

In a karstic area affected by acid mine drainage (AMD), hydrochemical conditions, such as temperature, salinity, alkalinity, DIC, dissolved oxygen, and nutrients, may affect the buffering capacity of carbonate systems in freshwater systems. The resulting pH fluctuation is larger than that of a marine system. Therefore, this study focuses on the buffering of a riverine carbonate system under the input of AMD and discusses the variations in a series of buffering factors, including the Revelle factor, γDIC, γAlk βDIC, βAlk, ωDIC, and ωAlk. The results revealed that the Revelle factor could reflect the buffering process effectively; in addition, the maximum value of the Revelle factor appeared at pH = 8.5. The data points for pH greater than this value indicated that the Huatan River had the ability to absorb atmospheric CO2 in spring. Conversely, the data for pH less than this value reflected the buffering of H+ during CO2 degassing in summer and autumn. In winter, the data were around the maximum value, indicating the weakest buffering capacity. As a result, the dynamics of the carbonate system caused the most sensitive response to pH. In addition, the maximum Revelle factor value did not always indicate the carbonate system had reached equilibrium; the presence of strong CO2 degassing was still a possibility. Under acidic conditions, as CO2(aq) increased, the absolute values of γDIC, βDIC, ωDIC, and γAlk increased correspondingly, indicating the enhanced buffering capacity of H+ during CO2 degassing. Under the four Representative Concentration Pathways scenarios (RCPs) included in the IPCC’s fifth assessment report, the degassing rate of the Huatan River would decrease by 5%, 15%, 26%, or 48%, depending on the scenario. Even though the Huatan River revealed CO2 degassing characteristics in winter and spring under current conditions, it will eventually become a sink for atmospheric CO2 as atmospheric CO2 concentration increases. In this light, the carbon sink effect in karst areas will become increasingly important.

ObjectiveVocal fold nodules (VFNs) are benign lesions, occurring at the junction of the anterior and middle thirds of bilateral vocal cords, for which pediatric prognosis and treatment remains controversial. There is a requirement for a correlation indicator to assess the prognosis by pediatric otolaryngologists.Materials and methodsPatients with VFNs, who were admitted to the department of otolaryngology, were enrolled. The patient’s gender, age, duration of dysphonia, laryngoscopy results and related diseases [allergic rhinitis, sinusitis, laryngopharyngeal reflux (LPR)] were collected and recovery from dysphonia followed up. Correlations between clinical factors and type of laryngoscopic morphology of VFNs were analyzed.ResultsA total of 432 patients with dysphonia were identified, 208 agreed to undergo laryngoscopy and 194 were diagnosed with VFNs as a result. The modal age of patients with dysphonia was between 3 and 7 years with a male: female ratio of 2.1:1 (294:138) and 116 (26.85%; 116/432) had symptoms of allergic rhinitis. The boy to girl ratio among the 194 children with VFNs was about 2.6:1 (140:54) and modal age was consistent with dysphonia. Vocal nodules were the cause of most phonation disorders (93.27%; 194/208) and those with long duration of dysphonia presented more mature (p = 0.026) and discrete types (p = 0.022). Boys were more likely to have mature (p = 0.050) and discrete nodules (p = 0.008). Dysphonia recovery time was closely related to age (p = 0.000), duration of dysphonia (p = 0.000) and morphology of vocal nodules under laryngoscopy (p = 0.000).ConclusionVocal nodules are the most frequent cause of phonation disorders in children. The morphological classification by endoscopy may help with clinical diagnosis and therapy choice. In the case of the older child with longer duration of dysphonia and the appearance of mature, large, discrete nodules by laryngoscopy, active treatment is recommended, such as drug therapy, voice therapy or surgical treatment.

Abstract Background Metacaspases are multifunctional proteins found in plants, fungi and protozoa, and are involved in processes such as insoluble protein aggregate clearance and cell proliferation. Our previous study demonstrated that metacaspase-1 (MCA1) contributes to parasite apoptosis in Toxoplasma gondii. Deletion of MCA1 from T. gondii has no effect on the growth and virulence of the parasites. Three metacaspases were identified in the ToxoDB Toxoplasma Informatics Resource, and the function of metacaspase-2 (MCA2) and metacaspase-3 (MCA3) has not been demonstrated. Methods In this study, we constructed MCA1, MCA2 and MCA1/MCA2 transgenic strains from RHΔku80 (Δku80), including overexpressing strains and knockout strains, to clarify the function of MCA1 and MCA2 of T. gondii. Results MCA1 and MCA2 were distributed in the cytoplasm with punctuated aggregation, and part of the punctuated aggregation of MCA1 and MCA2 was localized on the inner membrane complex of T. gondii. The proliferation of the MCA1/MCA2 double-knockout strain was significantly reduced; however, the two single knockout strains (MCA1 knockout strain and MCA2 knockout strain) exhibited normal growth rates as compared to the parental strain, Δku80. In addition, endodyogeny was impaired in the tachyzoites whose MCA1 and MCA2 were both deleted due to multiple nuclei and abnormal expression of IMC1. We further found that IMC1 of the double-knockout strain was detergent-soluble, indicating that MCA1 and MCA2 are associated with IMC1 maturation. Compared to the parental Δku80 strain, the double-knockout strain was more readily induced from tachyzoites to bradyzoites in vitro. Furthermore, the double-knockout strain was less pathogenic in mice and was able to develop bradyzoites in the brain, which formed cysts and established chronic infection. Conclusion MCA1 and MCA2 are important factors which participate in IMC1 maturation and endodyogeny of T. gondii. The double-knockout strain has slower proliferation and was able to develop bradyzoites both in vitro and in vivo. Graphic abstract

Introduction: The role of surgical drainage versus conservative therapy in treating patients with parapharyngeal abscesses is still a theme of debate. Objectives: This study aimed to investigate the characteristics associated with good outcomes in pediatric patients with parapharyngeal abscesses treated with conservative therapy. Methods: This retrospective chart review was performed on children aged 0.3–14 years with the diagnosis of parapharyngeal abscesses confirmed by computed tomography from January 2013 to March 2018. Patients with a severe upper airway obstruction required early intervention, while those in a stable condition initially received conservative therapy with antibiotics. If the patients appeared unlikely to recover, additional surgical drainage was provided. Multivariate logistic regression models were constructed to investigate the clinical characteristics associated with a good response to conservative therapy. A receiver operating characteristic curve was used to identify the age and abscess size cutoff for predicting a successful response. Results: A total of 48 children were included in the study. Patient age, antecedent illness, and abscess size were significantly associated with a response to therapy (Odds Ratio = 1.326, 2.314 and 1.235, respectively). The age cutoff associated with the conservative therapy was 4.2 years (76.9% sensitivity, 68.2% specificity), and the abscess size cutoff associated with the conservative therapy was 23 mm (84.6% sensitivity, 77.3% specificity). Conclusion: The findings suggested that younger age, smaller abscess size, and less frequent antecedent illnesses, such as upper respiratory tract infection and lymphadenitis, could predict a successful response to conservative therapy in pediatric patients with parapharyngeal abscesses.

To further explore the diagenetic environment, uranium precipitation mechanism and mineralization mechanism of the sandstone type uranium deposit in Sifangtai Formation on the southern margin of Daqing placanticline in Songliao Basin, the systematic research has been by drilling core observation, rock slice, sandstone uranium containing carbonate cement carbon and oxygen isotopic analysis of the sandstone rock types in the study area, the types of carbonate cements, diagenetic stage and systemic research on the carbon and oxygen isotopic been characteristics, The results show that the uraniferous sandstone rock types are feldspar lithic sandstone and lithic feldspar sandstone, carbonate cement being divided into three periods.For the first time and second time, the priority is given to cement, including calcite, ferroan calcite, see very small amounts of iron dolomite.The value of δ13CPDB is -22.45‰--13.65‰, with an average value of -18.00‰.The value of δ18OPDB is -17.56‰--9.46‰, with an average value of -13.52‰, revealing that there are some organic matters involved.The paleosalinity Z value is between 75.98 and 90.97, which is fresh water deposit.The paleotemperature is between 67.31℃ and 94.92℃, and the diagenetic environment is judged to be in the stage A of early-middle diagenesis based on the above rock features, cementite types and diagenesis.The comprehensive analysis shows that the compaction and cementation of the sadnstone during the early diagenesis stage reduce the porosity of the uranium-bearing sandstone and inhibits the migration of oxygen-rich uranium-bearing fluid.As diagenesis and bruial depth increase, higher organic matter maturity in the hot decarboxylate effect, and the compaction of adsorbed water to form acid solution were formed by dissolution of the feldspar, carbonate cement secondary pore, in order to increase sandstone porosity and promote oxygen rich fluid infiltration of uranium migration.Underlying oil and gas with upward dissipation through fracture provide stratum with reducing agent, making uranium be precipitated and enriched large scale at the bottom of Sifangtai Formation.

Cortical microtubules (MTs) in Apicomplexa are specialized MTs involved in maintaining the parasite’s shape and are, as such, unusually stable. Here, cryo-EM analysis of cortical MTs from Toxoplasma gondii offers insight into the mechanism of their stabilization by three bona fide microtubule inner proteins.