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BackgroundChina exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China’s pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks.MethodsRetrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny.ResultsVarious diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation.ConclusionThis investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19’s disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

IntroductionImproving photosynthetic use efficiency in dryland agroecosystems to sustain high agricultural yields is a key responsibility for ensuring food security.MethodsThis study was conducted in the regions on the semiarid Loess Plateau of China during 2018–2020. Dryland maize of Xianyu 335 comprised four modes: basic yield input (CK, plastic film mulching, 37500 plant.ha-1 of plant density and unfertilized), farmer input (FP, plastic film mulching, 45000 plant.ha-1 of plant density and inorganic nitrogen(N) and phosphate(P) fertilizer were 150kg.ha-1 and 90kg.ha-1), high yield and high-efficiency input (HH, full plastic-film mulching on double furrow, 67500 plant.ha-1 of plant density and N, P and organic manure(M) fertilizer were 230kg.ha-1, 140kg.ha-1 and 1500kg.ha-1), and super high yield input (SH, full plastic-film mulching on double furrow, 9000 plant.ha-1 of plant density and N, P and organic M fertilizer were 300kg.ha-1, 180kg.ha-1 and 7500kg.ha-1). The effects of different cultivation modes on yield, WUE, net photosynthetic rate(Pn), leaf area index(LAI), chlorophyll index(SPAD value) and root index were studied.ResultsThe results showed that the value average of yield and WUE for CK were 7790kg and 17480kg.ha-1 in three years. SH, HH and FP cultivation modes of yield and WUE was significant higher compared with CK cultivation mode (P

Clear aligner therapy is a rapidly developing orthodontic treatment. 3D-printing technology, which enables the creation of complex geometric structures with high precision, has been used in dentistry. This article aims to summarize the various aspects of 3D-printing clear aligners and give an outlook on their future development. The traditional thermoforming technology is introduced and the principle and application of 3D-printed clear aligners and materials are introduced, as well as the application prospects of 3D-printed clear aligners. According to PRISMA statement, the relevant literature of 3D-printing clear aligner was searched in PubMed, Web of Science, Embase and other databases. We searched the related words in the MESH database and then carried out advanced searches. We read systematic review and conference papers to find the articles related to the subject and manually added and excluded articles by reading the title and abstract. The production of clear aligners combines computer-aided 3D analysis, personalized design and digital molding technology. The thickness and edges of the 3D-printed clear aligner can be digitally controlled, which allows appliance more efficiently fitted. Presently, the array of clear resins suitable for 3D-printing include photo polymeric clear methacrylate-based resin (Dental LT) (Form Labs, Somerville, Mass), aliphatic vinyl ester-polyurethane polymer (Tera Harz TC-85) (Graphy, Seoul, South Korea). They all have good biocompatibility. But no such material is currently approved on the market. Developing biocompatible resins and further improving the material’s mechanical properties will be critical for the combination of 3D-printing and clear aligners. However, the literature on 3D-printed clear aligners is limited and lacks clinical application. Further in vivo and in vitro tests, as well as additional exploration in conjunction with corresponding cytological tests, are required for the research on available materials and machinery for 3D-printing clear aligners.

Mycoplasma bovis (M. bovis) is a significant bovine pathogen associated with various diseases, including bovine bronchopneumonia and mastitis resulting in substantial economic losses within the livestock industry. However, the development of effective control measures for M. bovis is hindered by a limited understanding of its virulence factors and pathogenesis. Nucleomodulins are newly identified secreted proteins of bacteria that internalize the host nuclei to regulate host cell gene expression and serve as critical virulence factors. Although recent reports have initiated exploration of mycoplasma nucleomodulins, the efficiency of conventional techniques for identification is very limited. Therefore, this study aimed to establish high-throughput methods to identify novel nucleomodulins of M. bovis. Using a direct biotinylation (DB) approach, a total of 289 proteins were identified including 66 high abundant proteins. In parallel, the use of proximity-based biotinylation (PBB), identified 28 proteins. Finally, seven nucleomodulins were verified to be nuclear by transfecting the bovine macrophage cell line BoMac with the plasmids encoding EGFP-fused proteins and observed with Opera Phenix, including the known nucleomodulin MbovP475 and six novel nucleomodulins. The novel nucleomodulins were four ribosomal proteins (MbovP599, MbovP678, MbovP710, and MbovP712), one transposase (MbovP790), and one conserved hypothetical protein (MbovP513). Among them, one unique nucleomodulin MbovP475 was identified with DB, two unique nucleomodulins (MbovP513 and MbovP710) with PBB, and four nucleomodulins by both. Overall, these findings established a foundation for further research on M. bovis nucleomodulin-host interactions for identification of new virulence factors.

ObjectiveTo examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects.MethodsThe effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition.ResultsFOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1β, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1β and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia–Shigella. Additionally, it promoted the production of acetic acid and propionic acid.ConclusionCompared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

BackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis (TB) and can be difficult to diagnose and treat. We aimed to describe the clinical presentation, diagnosis, disease spectrum, outcome, and prognostic factors of patients treated for TBM in China.MethodsA multicenter retrospective study was conducted from 2009 to 2019 enrolling all presumptive TBM patients referred to Xijing tertiary Hospital from 27 referral centers in and around Shaanxi province, China. Patients with clinical features suggestive of TBM (abnormal CSF parameters) were included in the study if they had adequate baseline information to be classified as “confirmed,” “probable,” or “possible” TBM according to international consensus TBM criteria and remained in follow-up. Patients with a confirmed alternative diagnosis or severe immune compromise were excluded. Clinical presentation, central nervous system imaging, cerebrospinal fluid (CSF) results, TBM score, and outcome—assessed using the modified Barthel disability index—were recorded and compared.FindingsA total of 341 presumptive TBM patients met selection criteria; 63 confirmed TBM (25 culture positive, 42 Xpert-MTB/RIF positive), 66 probable TBM, 163 possible TBM, and 49 “not TBM.” Death was associated with BMRC grade III (OR = 5.172; 95%CI: 2.298–11.641), TBM score ≥ 15 (OR = 3.843; 95%CI: 1.372–10.761), age > 60 years (OR = 3.566; 95%CI: 1.022–12.442), and CSF neutrophil ratio ≥ 25% (OR = 2.298; 95%CI: 1.027–5.139). Among those with confirmed TBM, nearly one-third (17/63, 27.0%) had a TBM score 60 years) have higher TBM scores or CSF neutrophil ratios, have signs of disseminated/miliary TB, and are at greatest risk of death. In general, more effort needs to be done to improve early diagnosis and treatment outcome in TBM patients.

Amino acid-derived quaternary ammonium salts were successfully applied in the asymmetric aza-Henry reaction of nitromethane to N-Boc trifluoromethyl ketimines. α-Trifluoromethyl β-nitroamines were synthesized in good to excellent yields with moderate to good enantioselectivities. This reaction is distinguished by its mild conditions, low catalyst loading (1 mol%), and catalytic base. It also proceeded on a gram scale without loss of enantioselectivity. The products were transformed to a series of adamantane-type compounds containing chiral trifluoromethylamine fragments. The potent anticancer activities of these compounds against liver cancer HepG2 and melanoma B16F10 were evaluated. Six promising compounds with notable efficacy have potential for further development.

Nuclear hydrogen production has the advantages of large-scale and low carbon emissions, and is expected to play an active role in the energy transition process. However, the storage and transportation of hydrogen pose potential risks of leakage and diffusion when connected to high-pressure hydrogen storage tanks and pipelines. To address this concern, this study focused on designing three distinct safety improvement schemes tailored for potential hydrogen leakage accidents. These schemes encompassed a passively distributed arrangement of obstacles (Scheme 1), a passively centralized arrangement of obstacles (Scheme 2), and an active fan array blowing (Scheme 3). Numerical simulation methods were applied on extensive spatial scales for relevant calculations. The results revealed that all three schemes effectively reduced the diffusion distance of combustible hydrogen. Specifically, at lower ambient wind speeds, Scheme 1, Scheme 2, and Scheme 3 achieved the shortest diffusion distances of 123 m, 56 m, and 46 m, respectively. Meanwhile, at higher ambient wind speeds, the corresponding distances were 282 m, 100 m, and 79 m. These results collectively offer valuable insights to mitigate the risk of leakage accidents in nuclear hydrogen production systems.

Aim: No information exists on the availability of pediatric medicines in China. This study aimed to access the availability of different types of pediatric medicine and determine their ratio in medical institution drug catalogs.Methods: Based on drug instructions, an expert meeting method was used to divide pediatric medicines into five categories: child-specific medicine (CSM), co-use medicine for adults and children (CMAC), other pediatric medicines (OCM), off-label medicine use (OMU), and non-child medicine (NM).Results: A total of 60 hospitals nationwide participated in this survey, namely, 20 children’s hospitals (C-hosp), 14 maternal and child healthcare hospitals (MCHC-hosp), and 26 general hospitals (G-hosp). The average number of drug catalogs in G-hosp was significantly higher than that in C-hosp and MCHC-hosp. CSM accounted for 9.77% of the C-hosp catalog, 7.12% of the MCHC-hosp catalog, and 1% of the G-hosp catalog. The availability rate of CMAC was 49.63% in C-hosp and 40.87% and 31% in MCHC-hosp and G-hosp, respectively. The proportion of OCM in C-hosp (27.28%) was higher than that in MCHC-hosp (13.4%) and G-hosp (5%). The OMU occupied ratio in C-hosp, MCHC-hosp, and G-hosp is not negligible, which was 12.06%, 8.7%, and 10% respectively. The proportion of NM in C-hosp was almost negligible but was 29.91% and 53% in MCHC-hosp and G-hosp, respectively. Compared to the CSM and CMAC listed in China, the share of CSM in C-hosp was close to 40%, which was much higher than that of G-hosp and MCHC-hosp. In contrast, the share of CMAC in G-hosp was nearly 30%, which was significantly higher than that in C-hosp and MCHC-hosp. Health insurance covers most of these five types of pediatric medicines, with the proportion of insured medicines reaching close to 80% in C-hosp and approximately 85% in MCHC-hosp and G-hosp.Discussion: The availability of specific medicines suitable for use in children is generally low, and even CSM in specialized hospitals such as C-hosp cannot meet the relatively high accessibility level of WHO evaluation standards. Policies and measures should be implemented to boost the research and development of pediatric medicines, as well as supplement safety information lacking in instruction manuals.

As we face increasing challenges of world food security and malnutrition, coarse cereals are coming into favor as an important supplement to human staple foods due to their high nutritional value. In addition, their functional components, such as flavonoids and polyphenols, make them an important food source for healthy diets. However, we lack a systematic understanding of the importance of coarse cereals for world food security and nutritional goals. This review summarizes the worldwide cultivation and distribution of coarse cereals, indicating that the global area for coarse cereal cultivation is steadily increasing. This paper also focuses on the special adaptive mechanisms of coarse cereals to drought and discusses the strategies to improve coarse cereal crop yields from the perspective of agricultural production systems. The future possibilities, challenges, and opportunities for coarse cereal production are summarized in the face of food security challenges, and new ideas for world coarse cereal production are suggested.

A fresh wave of technical change is seen as one of the most effective ways to achieve sustainable agricultural development due to the declining carrying capacity of resources and the environment. China, a nation with a sizable population, has drawn immense research attention over the following question: How can China promote agricultural transformation and achieve high-quality agricultural development through technological innovation? Based on the panel data that considers 28 provincial-level administrative regions in mainland China from 2010 to 2018, the study utilizes two-way fixed models; thus, it tests the impact of domestic agricultural research and development on high-quality agricultural development. Furthermore, it utilizes the moderating effect to verify the relationship between the two aforementioned factors under the influence of foreign technology introduction, human capital, and financial support. We observed the following: First, the high-quality agricultural development that characterized all the Chinese regions exhibited a steady upward trend. The industrial system, ecological system, and management system exhibited considerable development, whereas the development of the production system was lagging. Second, domestic agricultural research and development has promoted high-quality agricultural development. Third, under the moderating effect of foreign technology introduction, human capital, and financial support, the promotion effect of domestic agricultural research and development on high-quality agricultural development has gradually weakened. This study presents various proposals; thus, it strengthens the role of domestic agricultural research and development in promoting high-quality agricultural development.

Nucleotide second messengers play an important role in bacterial adaptation to environmental changes. Recent evidence suggests that some of these regulatory molecular pathways were conserved upon the degenerative evolution of the wall-less mycoplasmas. We have recently reported the occurrence of a phosphodiesterase (PDE) in the ruminant pathogen Mycoplasma bovis, which was involved in c-di-AMP metabolism. In the present study, we demonstrate that the genome of this mycoplasma species encodes a PDE of the GdpP family with atypical DHH domains. Characterization of M. bovis GdpP (MbovGdpP) revealed a multifunctional PDE with unusual nanoRNase and single-stranded DNase activities. The alarmone ppGpp was found unable to inhibit c-di-NMP degradation by MbovGdpP but efficiently blocked its nanoRNase activity. Remarkably, MbovGdpP was found critical for the osmotic tolerance of M. bovis under K+ and Na+ conditions. Transcriptomic analyses further revealed the biological importance of MbovGdpP in tRNA biosynthesis, pyruvate metabolism, and several steps in genetic information processing. This study is an important step in understanding the role of PDE and nucleotide second messengers in the biology of a minimal bacterial pathogen.

BackgroundAccording to a recent report by the WHO, approximately 17.5\% (about one-sixth) of the global adult population is affected by infertility. Consequently, researchers worldwide have proposed various machine learning models to improve the prediction of clinical pregnancy outcomes during IVF cycles. The objective of this study is to develop a machine learning(ML) model that predicts the outcomes of pregnancies following in vitro fertilization (IVF) and assists in clinical treatment.MethodsThis study conducted a retrospective analysis on provincial reproductive centers in China from March 2020 to March 2021, utilizing 13 selected features. The algorithms used included XGBoost, LightGBM, KNN, Naïve Bayes, Random Forest, and Decision Tree. The results were evaluated using performance metrics such as precision, recall, F1-score, accuracy and AUC, employing five-fold cross-validation repeated five times.ResultsAmong the models, LightGBM achieved the best performance, with an accuracy of 92.31%, recall of 87.80%, F1-score of 90.00\%, and an AUC of 90.41%. The model identified the estrogen concentration at the HCG injection(etwo), endometrium thickness (mm) on HCG day(EM TNK), years of infertility(Years), and body mass index(BMI) as the most important features.ConclusionThis study successfully demonstrates the LightGBM model has the best predictive effect on pregnancy outcomes during IVF cycles. Additionally, etwo was found to be the most significant predictor for successful IVF compared to other variables. This machine learning approach has the potential to assist fertility specialists in providing counseling and adjusting treatment strategies for patients.

To implement state policies of zero-markup drug policy and medical service fee adjustment for public hospitals, this study constructed game models of the pharmaceutical supply chain, consisting of a drug supplier and a public hospital. The study obtained the optimal medical service level and pricing under the new state drug policies. In addition, it analyzed the impacts of the degree of public benefit of hospitals on the medical service level, the medical service price, and the drug price. Finally, from the perspective of cooperation between drug suppliers and public hospitals, the specialized coordination contract was designed to maximize overall social welfare. This study found an anomalous but meaningful conclusion: in the background of the zero-markup drug policy, a higher public benefit of hospitals could increase the drug prices, but it could reduce the medical service prices further to cut down on the overall treatment fees for the patients. The novel coordination contract can optimize the pharmaceutical supply chain and achieve a win-win situation for the drug suppliers, public hospitals, and patients. When the public benefit of hospitals is higher, the profit of a decentralized decision-making supply chain is greater than a centralized one, while the pharmaceutical supply chain will not coordinate itself.

Brucellosis is considered one of the most hazardous zoonotic diseases all over the world. It causes formidable economic losses in developed and developing countries. Despite the significant attempts to get rid of Brucella pathogens in many parts of the world, the disease continues to spread widely. Recently, many attempts proved to be effective for the prevention and control of highly contagious bovine brucellosis, which could be followed by others to achieve a prosperous future without rampant Brucella pathogens. In this study, the updated view for worldwide Brucella distribution, possible predisposing factors for emerging Brucella pathogens, immune response and different types of Brucella vaccines, genomics and proteomics approaches incorporated recently in the field of brucellosis, and future perspectives for prevention and control of bovine brucellosis have been discussed comprehensively. So, the current study will be used as a guide for researchers in planning their future work, which will pave the way for a new world without these highly contagious pathogens that have been infecting and threatening the health of humans and terrestrial animals.

Solar spicules are small-scale jet-like structures in the lower solar atmosphere. Currently, the formation of these widely distributed structures lacks a complete explanation. It is still unclear whether they play an essential role in corona heating. Here, based on the magnetohydrodynamic scaling transformation relation, we perform experiments with the interaction of a high power laser with a one-dimensional sinusoidal modulated target to model solar spicules. We observe several spicule-like structures with alternating polarity magnetic fields around them. Magnetohydrodynamic simulations with similar parameters show the detail information during the spicules’ formation. The results suggest that the so-called strong pulse model can lead to the formation of the solar spicules. The magnetic reconnection process may also play a part and lead to additional heating and brightening phenomena.

IntroductionOwing to urbanization, living habits have changed widely, leading to alterations in the intestinal microbiota of urban residents. However, there are few studies on the characteristics of intestinal microbiota of adolescents living in different urbanized areas in China.MethodsA total of 302 fecal samples collected from adolescent students in eastern China were examined. 16S rRNA high-throughput sequencing was used to identify the fecal microbiota. These data were combined with questionnaire survey results to investigate the effect of urbanization on the intestinal microbiota of adolescents in eastern China. Moreover, the role of lifestyle habits in this relationship was also evaluated.ResultsThe results revealed significant differences in the structure of the intestinal microbiota among adolescents living in regions with different levels of urbanization. Adolescents living in urban regions had a significantly higher proportion of Bacteroides (p < 0.001, FDR = 0.004), whereas those living in towns and rural regions had higher proportions of Bifidobacterium (p < 0.001, FDR

Mycoplasmas are successful pathogens that cause debilitating diseases in humans and various animal hosts. Despite the exceptionally streamlined genomes, mycoplasmas have evolved specific mechanisms to access essential nutrients from host cells. The paucity of genetic tools to manipulate mycoplasma genomes has impeded studies of the virulence factors of pathogenic species and mechanisms to access nutrients. This review summarizes several strategies for editing of mycoplasma genomes, including homologous recombination, transposons, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, and synthetic biology. In addition, the mechanisms and features of different tools are discussed to provide references and future directions for efficient manipulation of mycoplasma genomes.

BackgroundThe spatial distribution of tumor-infiltrating T cells and its dynamics during chemoradiotherapy combined with PD-1 blockade is little known in esophageal squamous cell carcinoma (ESCC).MethodsWe applied the multiplex immunofluorescence method to identify T cells (CD4+, CD8+ T cells, and their PD-1− or PD-1+ subsets) and myeloid-derived cells (CD11c+ dendritic cells, CD68+ macrophages, and their PD-L1+ subpopulations) in paired tumor biopsies (n = 36) collected at baseline and during combination (40 Gy of radiation) from a phase Ib trial (NCT03671265) of ESCC patients treated with first-line chemoradiotherapy plus anti-PD-1 antibody camrelizumab. We used the FoundationOne CDx assay to evaluate tumor mutational burden (TMB) in baseline tumor biopsies (n = 14). We dynamically assessed the nearest distance and proximity of T-cell subsets to tumor cells under combination and estimated the association between T-cell spatial distribution and combination outcome, myeloid-derived subsets, TMB, and patient baseline characteristics.FindingsWe found that the tumor compartment had lower T-cell subsets than the stromal compartment but maintained a comparable level under combination. Both before and under combination, PD-1− T cells were located closer than PD-1+ T cells to tumor cells; T cells, dendritic cells, and macrophages showed the highest accumulation in the 5–10-μm distance. Higher CD4+ T cells in the tumor compartment and a shorter nearest distance of T-cell subsets at baseline predicted poor OS. Higher baseline CD4+ T cells, dendritic cells, and macrophages were associated with worse OS in less than 10-μm distance to tumor cells, but related with better OS in the farther distance. Higher on-treatment PD-1-positive-expressed CD4+ and CD8+ T cells within the 100-μm distance to tumor cells predicted longer OS. T cells, dendritic cells, and macrophages showed a positive spatial correlation. Both high TMB and smoking history were associated with a closer location of T cells to tumor cells at baseline.ConclusionsWe firstly illustrated the T-cell spatial distribution in ESCC. Combining chemoradiotherapy with PD-1 blockade could improve the antitumor immune microenvironment, which benefits the treatment outcome. Further understanding the precision spatiality of tumor-infiltrating T cells would provide new evidence for the tumor immune microenvironment and for the combination treatment with immunotherapy.

BackgroundOver the years, endoscopic carpal tunnel release (ECTR) has gained significant interest as an alternative to surgery. However, no consensus has been reached on the necessity of postoperative wrist immobilization. This study aims to compare the outcomes of wrist immobilization for a period of 2 weeks to immediate wrist mobilization after ECTR.MethodsA total of 24 patients with idiopathic carpal tunnel syndrome undergoing dual-portal ECTR from May 2020 to Feb 2022 were enrolled and randomly divided into two groups postoperatively. In one group, patients wore a wrist splint for 2 weeks. In another group, wrist mobilization was allowed immediately after surgery. The two-point discrimination test (2PD test); the Semmes–Weinstein monofilament test (SWM test); the occurrence of pillar pain, digital and wrist range of motion (ROM); grip and pinch strength; the visual analog score (VAS), the Boston Carpal Tunnel Questionnaire (BCTQ) score; the Disabilities of the Arm, Shoulder, and Hand (DASH) score; and complications were evaluated at 2 weeks and 1, 2, 3, and 6 months after the surgery.ResultsAll 24 subjects finished this study with no dropouts. During the early follow-up, patients with wrist immobilization demonstrated lower VAS scores, lower occurrence of pillar pain, and higher grip and pinch strength compared with the immediate mobilization group. No significant difference was obtained between these two groups in terms of the 2PD test, the SWM test, digital and wrist ROM, BCTQ, and the DASH score. In total, two patients without splints reported transient scar discomfort. No one complained of neurapraxia, injury of the flexor tendon, median nerve, and major artery. At the final follow-up, no significant difference was found in any parameters between both groups. The local scar discomfort mentioned above disappeared and left no serious sequela.ConclusionWrist immobilization during the early postoperative period demonstrated significant pain alleviation along with stronger grip and pinch strength. However, wrist immobilization yielded no obvious superiority regarding clinical outcomes at the final follow-up.

Background and purposeThe first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients.Materials and methodsThe BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4 mg/min) given continuously for 20 min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b.ResultsThe first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%, p = 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%, p = 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%, p = 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%, p = 0.11).ConclusionThis is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.

IntroductionThis study aimed to investigate the incidence of deep vein thrombosis (DVT) in patients with pelvic or lower-extremity fractures in the emergency intensive care unit (EICU), explore the independent risk factors for DVT, and investigate the predictive value of the Autar scale for DVT in these patients.MethodsThe clinical data of patients with single fractures of the pelvis, femur, or tibia in the EICU from August 2016 to August 2019 were retrospectively examined. The incidence of DVT was statistically analyzed. Logistic regression was used to analyze the independent risk factors for DVT in these patients. The receiver-operating characteristic (ROC) curve was used to evaluate the predictive value of the Autar scale for the risk of DVT.ResultsA total of 817 patients were enrolled in this study; of these, 142 (17.38%) had DVT. Significant differences were found in the incidence of DVT among the pelvic fractures, femoral fractures, and tibial fractures (P

AimVaccination is one of the most effective strategies to contain the transmission of infectious diseases; however, people's intentions and behavior for vaccination vary across different regions and countries around the world. It is not clear how socioecological factors such as residential mobility influence people's vaccination behaviors for infectious diseases.MethodsWe analyzed public data on residential mobility and vaccination rates for COVID-19 and seasonal flu in the United States and explored how residential mobility in the previous year influenced vaccination rates for COVID-19 and seasonal flu (2011–2018) across 50 states of the US. The data were accessed and analyzed in 2021.ResultsStudy 1 demonstrated that collective-level residential mobility predicted COVID-19 vaccination rates across the United States (B = −168.162, 95% CI [−307.097, −29.227], adjusted R2 = 0.091, p = 0.019). Study 2 corroborated this finding by documenting that collective-level residential mobility predicted vaccination rates for seasonal flu from 2011 to 2018 across the United States (B = −0.789, 95% CI = [−1.018, −0.56], adjusted R2 = 0.222, p < 0.001). The link between residential mobility and vaccination behavior was robust after controlling relevant variables, including collectivism, cultural tightness–looseness, and sociodemographic variables.ConclusionsOur research demonstrated that residential mobility is an important socioecological factor that influences people's vaccination behaviors for COVID-19 and seasonal flu. The results enrich our understanding of the socioecological factors that influence vaccination behaviors and have implications for developing tailored interventions to promote vaccination during pandemics of infectious diseases.

IntroductionDuring COVID-19, some front-line personnel experienced varying degrees of eye discomfort due to the use of goggles repeatedly disinfected with chlorine-containing disinfectant.MethodsThe eye damage information of 276 front-line personnel who used goggles in a hospital from October 1, 2021, to December 1, 2021, was collected by filling out a questionnaire. To study the effect of chlorinated disinfectants on goggles, we immersed the goggles in the same volume of water and chlorinated disinfectant buckets. We tested the light transmittance, color and texture, and airtightness of the goggles at different times (1, 3, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168, 192, 216, 240, and 268 h). In addition, we detected where chlorinated disinfectant remained in the goggles by using disinfectant concentration test paper.Results60 (21.82%) people experienced dry eyes, stinging pain, photophobia and tearing, conjunctival congestion, eyelid redness, and swelling. After treatment or rest, the patient's ocular symptoms were significantly relieved within 3 days. With the extension of disinfection time, the light transmission of the lenses gradually decreased, and the light transmission reduced when immersion occurred at 216 h. After 72 h of disinfection, the color of the goggle frame began to change to light yellow, the texture gradually became hard and brittle, and the color became significantly darker at 268 h of disinfection. The airtightness of the goggles began to decrease after 168 h of disinfection, the airtightness decreased substantially at 268 h, and the shape changed significantly. In addition, the concentration test paper results show that the disinfection solution mainly resides in the goggle frame seam and goggles' elastic bands' bundle.ConclusionsRepeated chlorine disinfectant disinfection will reduce the effectiveness of goggles protection and damage front-line personnel's eye health.

The dried leaves of Eucommia ulmoides Oliv., which have a high nutritional value, are mainly used in both medicine and food. In this study, we used Eucommia ulmoides leaf superfine powder as an additive in the fermentation of glutinous rice (Semen Oryzae Glutinosae) to develop a new healthcare product, Eucommia leaf sweet rice wine. The fermentation conditions were optimized, and the nutrient value was evaluated through analyses of metabolites, functional compositions, antioxidant capacity, and antihyperglycemic, antihyperlipidemic, and antihypertensive abilities. The metabolic analysis demonstrated that Eucommia leaf sweet rice wine contained a large number of flavonoids and other metabolites. Eucommia leaf sweet rice wine had higher contents of flavonoid (729.0 ± 0.11 μg/g), free amino acids (55.0 ± 0.37 μg/g), polyphenol (150.0 ± 0.43 μg/g), and polysaccharide (0.25 ± 0.03 μg/g) than traditional sweet rice wine, with increases of 14.7, 2.6, 6.8, and 6.3 times, respectively. In addition, an analysis of antioxidant capacity in vitro revealed that Eucommia leaf sweet rice wine had a high level of activity in scavenging 2, 2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, and hydroxyl radicals, as well as in reducing iron, indicating that it was a strong antioxidant. Furthermore, Eucommia leaf sweet rice wine had a high cholate binding capacity and could significantly inhibit α-amylase, α-glucosidase, and angiotensin-converting enzyme (ACE) activity. In conclusion, this study developed a new application of Eucommia leaf in sweet rice wine fermentation and brewed Eucommia leaf sweet rice wine with strong antioxidant activity and positive antihypertensive, antihyperglycemic, and antihyperlipidemic effects in vitro. This study suggests new opportunities for the wider use of Eucommia ulmoides leaves and adds variety to sweet rice wine.

IntroductionLiver transplantation is a risk factor for premalignant and malignant changes of the duodenum. De novo duodenal malignancy is seldom reported after liver transplantation.Case ReportThe present study reports a case of an asymptomatic 67-year-old male patient who underwent liver transplantation more than 10 years ago and subsequently developed duodenal malignancy. Endoscopic biopsy of the de novo duodenal malignancy indicated duodenal carcinoma and pancreatoduodenectomy (PD) was performed. The patient was successfully discharged 12 days after the surgery. A metastatic lesion occurred at the right seventh rib 14 months after the pancreatoduodenectomy. Postoperative pathological examination indicated hepatocellular carcinoma metastasis.ConclusionsTo the best of our knowledge, this case type has not been previously reported. The present study sheds light on the development, the treatment, the prognosis, and the management of a new type of de novo duodenal malignancy.

Titanium and Titanium alloys are widely used as biomedical implants in oral and maxillofacial surgery, due to superior mechanical properties and biocompatibility. In specific clinical populations such as the elderly, diabetics and patients with metabolic diseases, the failure rate of medical metal implants is increased significantly, putting them at increased risk of revision surgery. Many studies show that the content of reactive oxygen species (ROS) in the microenvironment of bone tissue surrounding implant materials is increased in patients undergoing revision surgery. In addition, the size and shape of materials, the morphology, wettability, mechanical properties, and other properties play significant roles in the production of ROS. The accumulated ROS break the original balance of oxidation and anti-oxidation, resulting in host oxidative stress. It may accelerate implant degradation mainly by activating inflammatory cells. Peri-implantitis usually leads to a loss of bone mass around the implant, which tends to affect the long-term stability and longevity of implant. Therefore, a great deal of research is urgently needed to focus on developing antibacterial technologies. The addition of active elements to biomedical titanium and titanium alloys greatly reduce the risk of postoperative infection in patients. Besides, innovative technologies are developing new biomaterials surfaces conferring anti-infective properties that rely on the production of ROS. It can be considered that ROS may act as a messenger substance for the communication between the host and the implanted material, which run through the entire wound repair process and play a role that cannot be ignored. It is necessary to understand the interaction between oxidative stress and materials, the effects of oxidative stress products on osseointegration and implant life as well as ROS-induced bactericidal activity. This helps to facilitate the development of a new generation of well-biocompatible implant materials with ROS responsiveness, and ultimately prolong the lifespan of implants.

The abnormal function of striatal medium spiny neurons (MSNs) leads to the excitation-inhibition imbalance of the basal ganglia, which is an important pathogenic factor of Parkinson’s disease (PD). Exercise improves the dysfunction of basal ganglia through neuroprotective and neuroreparative effects, which may be related to the functional changes of expresses D2 receptors MSNs (D2-MSNs). In this study, D2-Cre mice were selected as the research objects, the PD model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA) in the striatum, and the 4-week treadmill training method was used for exercise intervention. Using optogenetics and behavioral tests, we determined that the average total movement distance of PD and PD + Ex groups was significantly lower than that of the Control group, while that of the PD + Ex and PD + Laser groups was significantly higher than that of the PD group, and the two intervention methods of exercise and optogenetic-stimulation of the D2-MSNs had basically similar effects on improving the autonomic behavior of PD mice. To further investigate the cellular mechanisms, whole-cell patch clamp recordings were carried out on D2-MSNs. We found that exercise decreased the frequency and amplitude of spontaneous excitatory postsynaptic current (sEPSC) and increased the paired-pulse radio of D2-MSNs while leaving basic electrophysiological properties of MSNs unaffected. Combined with behavioral improvement and enhanced D2R protein expression, our findings suggest the inhibited sEPSC of D2-MSNs may contribute to the behavioral improvement after exercise.

Green finance is an important practice of China’s high-quality economic development in the new era, which is closely related to economic development, environment, and energy conditions. However, few studies systematically analyze the impact of green finance on economic development, environmental pollution, and energy consumption, especially on China which is turning to high-quality economic development. In order to fill the gap, based on the annual data on 30 provinces (autonomous regions and municipalities) in China from 2008 to 2018, we construct a comparatively comprehensive green finance index system and use a panel regression model to explore the impacts of green finance on high-quality economic development, environmental pollution, and energy consumption. We find that green finance can significantly promote high-quality economic development, mitigate environmental pollution, and reduce energy consumption. There is spatial and temporal heterogeneity in the impact of green finance on China’s economic quality, environmental pollution, and energy consumption. In the eastern region, green finance has a remarkable positive impact on high-quality economic development and a significant negative impact on energy consumption, but the impact on environmental pollution is inconspicuous. In the central region, green finance has a prominent effect on reducing environmental pollution, but the impact on high-quality economic development and energy consumption is not significant. In the western region, green finance has not been able to significantly promote high-quality economic development, mitigate environmental pollution, and reduce energy consumption. After the clear proposal of green finance, the role of green finance in promoting a high-quality economy has enhanced, and the role of green finance in reducing environmental pollution and energy consumption has decreased. This study can provide a useful decision-making reference for promoting high-quality economic development, reducing environmental pollution and energy consumption, and spurring sustainable development.

FOXP3+ regulatory T (Treg) cells play critical roles in establishing the immunosuppressive tumour microenvironment, which is achieved and dynamically maintained with the contribution of various stromal and immune cell subsets. However, the dynamics of non-lymphoid FOXP3+ Treg cells and the mutual regulation of Treg cells and other cell types in solid tumour microenvironment remains largely unclear. In this review, we summarize the latest findings on the dynamic connections and reciprocal regulations of non-lymphoid Treg cell subsets in accordance with well-established and new emerging hallmarks of cancer, especially on the immune escape of tumour cells in solid tumours. Our comprehension of the interplay between FOXP3+ Treg cells and key hallmarks of cancer may provide new insights into the development of next-generation engineered T cell-based immune treatments for solid tumours.

Rapid industrialization and urbanization have caused serious cadmium (Cd) pollution in soil. Tartary buckwheat is an important pseudocereal crop with the potential ability to tolerate various stresses. However, the responses to Cd stress in this species are unclear. In this study, we assessed the phenotypic, cytological, physiological, and transcriptomic characteristics of Tartary buckwheat under the various concentrations of Cd treatments to investigate the responses and their regulatory pathways for the first time. The results showed Tartary buckwheat could tolerate the high Cd concentration of 50 mg/L under Cd stress. The average root diameters increased as a result of more cell layers of the endodermis and the bigger size of the pericycle. Cd primarily accumulated in roots and relatively less transferred to leaves. Antioxidant activities and malondialdehyde (MDA) accumulation varied in different tissues and different Cd concentrations of treatments. Meanwhile, Cd stress led to the formation of Casparian strips in roots and damaged the cytoderm and organelles. The weighted gene co-expression and interaction network analyses revealed that 9 core genes induced by Cd stress were involved in metal ion binding, Ca signal transduction, cell wall organization, antioxidant activities, carbohydrate metabolic process, DNA catabolic process, and plant senescence, which regulated a series of phenotypic, cytological, and physiological changes above. These results laid the foundation for a deep understanding of the responses to Cd toxicity in Tartary buckwheat. It’s also a critical reference for the functional characterization of genes for Cd tolerance.

Eucommia ulmoides Oliv. (Duzhong), a valued traditional herbal medicine in China, is rich in antibacterial proteins and is effective against a variety of plant pathogens. Fusarium oxysporum is a pathogenic fungus that infects plant roots, resulting in the death of the plant. In this study, transcriptomic and proteomic analyses were used to explore the molecular mechanism of E. ulmoides counteracts F. oxysporum infection. Transcriptomic analysis at 24, 48, 72, and 96 h after inoculation identified 17, 591, 1,205, and 625 differentially expressed genes (DEGs), while proteomics identified were 66, 138, 148, 234 differentially expressed proteins (DEPs). Meanwhile, GO and KEGG enrichment analyses of the DEGs and DEPs showed that they were mainly associated with endoplasmic reticulum (ER), fructose and mannose metabolism, protein processing in the ER, type II diabetes mellitus, the ribosome, antigen processing and presentation, and the phagosome. In addition, proteome and transcriptome association analysis and RT-qPCR showed that the response of E. ulmoides to F. oxysporum was likely related to the unfolded protein response (UPR) of the ER pathway. In conclusion, our study provided a theoretical basis for the control of F. oxysporum.

Post-traumatic stress disorder (PTSD) can develop after stroke attacks, and its rate ranges from 4 to 37% in the stroke population. Suffering from PTSD not only decreases stroke patient’s quality of life, but also relates to their non-adherence of treatment. Since strokes often recur and progress, long-term medical management is especially important. However, previous studies generally focused on the epidemiological characteristics of post-stroke PTSD, while there are literally no studies on the psychological intervention. In our study, 170 patients with a first-ever stroke during the acute phase were recruited. They were randomized into Psycho-therapy group 1 and Control group 1, and were administered with preventive intervention for PTSD or routine health education, respectively. At 2-month follow-up, PTSD symptoms were evaluated. Participants who were diagnosed with post-stroke PTSD were further randomized into Psycho-therapy group 2 and Control group 2, and received supportive therapy or routine health counseling, respectively. At 6-month follow-up (1°month after the therapy was completed), PTSD symptoms were re-evaluated. Our results showed that at 2-month, the PTSD incidence in our series was 11.69%, and the severity of stroke was the only risk factor for PTSD development. The preventive intervention was not superior to routine health education for PTSD prevention. At 6-month, results indicated the supportive therapy did have a fine effect in ameliorating symptoms for diagnosed PTSD patients, superior to routine health counseling. Thus, our study was the first to provide evidence that the supportive therapy was effective in treating post-stroke PTSD early after its diagnosis. This clinical trial was preregistered on www.chictr.org.cn (ChiCTR2100048411).

Mycoplasma bovis (M. bovis) is an important pathogen of the bovine respiratory disease complex, invading lower respiratory tracts and causing severe pneumonia. However, its molecular mechanism largely remains unknown. Host annexin A2 (ANXA2) is a calcium-dependent phospholipid-binding protein. The current study sought to determine whether ANXA2 could mediate M. bovis adhesion and invasion thereby affecting its induction of inflammatory response. ANXA2 expression was upregulated in M. bovis-infected bovine lung epithelial cells (EBL), and blocking ANXA2 with an anti-ANXA2 antibody reduced M. bovis adhesion to EBL. Compared with uninfected cells, more ANXA2 was translocated from the cytoplasm to the cell surface after M. bovis infection. Furthermore, RNA interference knockdown of ANXA2 expression in EBL cells resulted in a significant decrease in M. bovis invasion and F-actin polymerization. Next, the transcriptomic study of M. bovis-infected EBL cells with and without ANXA2 knockdown were performed. The data exhibited that ANXA2 knockdown EBL cells had 2487 differentially expressed genes (DEGs), with 1175 upregulated and 1312 downregulated compared to control. According to GO and KEGG analyses, 50 genes potentially linked to inflammatory responses, 23 involved in extracellular matrix (ECM) receptor interaction, and 48 associated with PI3K-AKT signal pathways were upregulated, while 38 mRNA binding genes, 16 mRNA 3′-UTR binding genes, and 34 RNA transport genes were downregulated. Furthermore, 19 genes with various change-folds were selected for qPCR verification, and the results agreed with the RNA-seq findings. Above all, the transcription of two chemokines (IL-8 and CXCL5) and a key bovine β-defensin TAP in IL-17 signaling pathway were significantly increased in ANXA2 knockdown cells. Moreover, ANXA2 knockdown or knockout could increase NF-κB and MAPK phosphorylation activity in response to M. bovis infection. Additionally, ANXA2 knockdown also significantly decreased the CD44 transcripts via exon V3 and V7 skipping after M. bovis infection. We concluded that M. bovis borrowed host ANXA2 to mediate its adhesion and invasion thereby negatively regulating molecular expression essential to IL-17 signal pathway. Furthermore, CD44 V3 and V7 isoforms might contribute to this ANXA2 meditated processes in M. bovis infected EBL cells. These findings revealed a new understanding of pathogenesis for M. bovis infection.

ObjectivePoor sleep quality is highly prevalent in patients with chronic diarrheal symptoms or inflammatory bowel disease (IBD). This study aimed to evaluate the associations of chronic diarrheal symptoms and IBD with sleep quality in the general US population.Methods14,696 adults (≥20 years) from the National Health and Nutrition Examination Survey (2005–2010) were included in the study. Chronic diarrheal symptoms and IBD were defined by self-reports. Sleep quality was assessed by sleep disorder, sleep trouble, and sleep duration. Multivariable logistic regression models were used to examine the associations.ResultsAfter adjustment of a series of covariates, we found that participants with chronic diarrheal symptoms or IBD had higher odds of sleep disorder [chronic diarrheal symptoms: odds ratio (OR) = 1.20, 95% confidence interval (CI) = 1.04–1.38; IBD: OR = 3.86, 95% CI = 1.92–7.77] and sleep trouble (chronic diarrheal symptoms: OR = 1.19, 95% CI = 1.09–1.30; IBD: OR = 2.32, 95% CI = 1.30–4.14), respectively. Sleep duration for participants with IBD was significantly shorter than that for those without IBD (β = −0.39, 95% CI = −0.78 to 0.01, P = 0.045). Subgroup analyses revealed that the associations of chronic diarrheal symptoms and IBD with sleep disorder and sleep trouble were more pronounced among women.ConclusionsIn this large sample of US adults, we found that chronic diarrheal symptoms and IBD were significantly associated with sleep quality, particularly in women. The findings highlight the importance of managing bowel health to promote high quality of sleep; and thus, improve quality of life in this subpopulation.

Mycoplasma bovis (M. bovis) is one of the major pathogens in the bovine respiratory disease complex, which includes pneumonia, mastitis, and arthritis and causes a great economic loss in the cattle industry. In China, a live-attenuated vaccine strain M. bovis P150 was obtained by a continuous culture of the wild-type strain M. bovis HB0801 (P1) in vitro for 150 passages. Using the infected bovine macrophage cell line BoMac, this work attempted to investigate the mechanism of P150 attenuation and protective immune response. To begin, we show that M. bovis P150 effectively triggered cytotoxicity and apoptosis in BoMac, although with lower intracellular survival than P1. The transcriptomes of BoMac after infection with M. bovis strains P1 and P150 were sequenced, and bioinformatic analysis identified 233 differentially expressed genes (DEGs), with 185 upregulated and 48 downregulated. Further Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses revealed that the majority of the DEGs were linked to CHOP complex, MAP kinase phosphatase activity and were involved in the IL-17 signaling pathway in immune response, MAPK signaling pathway in signal transduction, and p53 signaling pathway in cell growth and death. Among them, the level of C/EBP homologous protein (CHOP) was significantly upregulated in P150-infected BoMac compared to P1-infected cells at different time points, along with its upstream and downstream genes phosphorylated-PERK, phosphorylated-EIF2α, ATF4, and GADD45A increased in the PERK-dependent ER stress response. The role of CHOP in apoptosis was further verified by M. bovis-induced siCHOP knockdown in BoMac cells. The results showed that CHOP knockdown enhanced P150-induced apoptosis and dramatically increased the M. bovis P1 and P150 intracellular survival, particularly for P150. These data suggest that P150 infection upregulates CHOP expression, which can increase apoptosis and mediate a crosstalk between ER stress and apoptosis during infection, and hence, contribute to high cytotoxicity and low intracellular survival.

Objective: Owing to the intensification of the aging process worldwide, the prevalence of adult degenerative scoliosis (ADS) is increasing at an alarming rate. However, genomic research related to the etiology of ADS is rarely reported worldwide. Since long noncoding RNAs (lncRNAs) play a pivotal role in the progression of human diseases, this study aimed to investigate ADS-associated messenger RNAs (mRNAs) and lncRNAs by RNA sequencing (RNA-seq), as well as performed comprehensive bioinformatics analysis based on the lncRNA–mRNA coexpression network and protein–protein interaction (PPI) network.Methods: Initially, six whole blood (WB) samples were obtained from three ADS and three nondegenerative lumbar trauma patients who underwent surgical operation for RNA-seq exploration to construct differential mRNA and lncRNA expression profiles. Subsequently, quantitative RT-PCR (qRT-PCR) was performed to validate three randomly selected differentially expressed mRNAs and lncRNAs derived from the nucleus pulposus (NP) tissue of 14 other subjects (seven ADS patients and seven nondegenerative lumbar trauma patients), respectively.Results: A total of 1,651 upregulated and 1,524 downregulated mRNAs and 147 upregulated and 83 downregulated lncRNAs were screened out from the RNA-Seq data, which constructed coexpression networks to investigate their regulatory interactions further. GO gene function prediction revealed that lncRNA-targeted genes might play a vital role in ADS via participation in multiple biological processes such as the AMPK signaling pathway, lysosomes, and ubiquitin-mediated proteolysis, as well as cellular metabolic processes. Moreover, the expression levels of three selected lncRNAs and mRNAs were validated by qRT-PCR, respectively, demonstrating that the relative expression levels were consistent with the RNA-seq data. Notably, the dysregulated RNAs, AKT1, UBA52, PTPN12, and CLEC16A, were significantly differentially expressed in ADS WB samples and might serve as potentially regulated genes for research in the future.Conclusions: This study provides the first insight into the altered transcriptome profile of long-stranded noncoding RNAs associated with ADS, which paves the way for further exploration of the clinical biomarkers and molecular regulatory mechanisms for this poorly understood degenerative disease. However, the detailed biological mechanisms underlying these candidate lncRNAs in ADS necessitate further elucidation in future studies.

Mobile health (mHealth) services have been widely used in medical services and health management through mobile devices and multiple channels, such as smartphones, wearable equipment, healthcare applications (Apps), and medical platforms. However, the number of the users who are currently receiving the mHealth services is small. In China, more than 70% of internet users have never used mHealth services. Such imbalanced situation could be attributed to users’ traditional concept of medical treatment, psychological factors (such as low self-efficacy) and privacy concerns. The purpose of this study is to explore the direct and indirect effects of mHealth users’ self-efficacy and privacy concerns on their intention to adopt mHealth services, providing guidelines for mHealth service providers to enhance users’ intention of adoption. A questionnaire was designed by the research team and 386 valid responses were collected from domestic participants in China. Based on the unified theory of acceptance and use of technology (UTAUT) model, a research model integrated self-efficacy and privacy concerns was constructed to investigate their effects on users’ intention to adopt mobile mHealth services. The results show that self-efficacy could facilitate users’ intention to adopt mHealth services, and had a significantly positive effect on perceived ubiquity, effort expectancy, performance expectancy and subjective norm. This study verifies the direct and indirect effects of self-efficacy and privacy concerns on users’ intention to adopt mHealth services, providing a different perspective for studying mHealth adoption behavior. The findings could provide guidelines for mHealth service providers to improve their service quality and enhance users’ intention of adoption.

PurposePrimary sporadic intradural malignant peripheral nerve sheath tumor (MPNST) in the spinal canal is a type of rare neoplasm with challenging diagnosis and therapy. The overall prognosis of this tumor is markedly different from that of the usual spinal intradural tumors. The purpose of this systematic review is to reduce the misdiagnosis and enhance the prognosis of the disease by reviewing the literature.MethodsPubMed, Medline, and Embase databases were searched for articles in English language published from 1980 to May 2021, yielding 500 potentially relevant articles. The keywords were as follows: “spinal”, “malignant peripheral nerve sheath tumor”, “neurosarcoma”, “malignant schwannoma”, and “malignant neurofibroma”. Thirteen papers met the eligibility criteria, including 55 cases with spinal intradural primary sporadic MPNSTs, which were confirmed by post-operation pathology. We further analyzed the clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis.ResultsFifty-five spinal intradural primary sporadic MPNSTs from 30 (54.5%) male and 25 (45.5%) female patients with an average age at diagnosis of 40 years (range, 3–70 years) were included in the study. The most common clinical manifestations were local or radicular pain and motor disturbance. All tumors had significant enhancement and heterogeneous enhancement was more common. Out of 18 lesions, 14 were diagnosed as high grade and the remaining 4 were diagnosed as low grade. The ki-67 labeling index ranged from 5% to 60%. The median recurrence and survival time were 36 and 72 months, respectively. The log-rank tests indicated that significant predictors of OS were patient age (≤30 vs. >30 years) at the time of diagnosis and the presence of metastatic disease, and similar analyses for RFS demonstrated that the presence of metastatic disease was the only significant predictor (60 vs. 10 months). The multivariate Cox proportional hazards regression analysis revealed that absence of metastasis was an independent factor for predicting a favorable prognosis.ConclusionsSpinal intradural primary sporadic MPNSTs are challenging malignant tumors without a systematic treatment plan. The factors affecting its prognosis are not clear. Even after surgical treatment and adjuvant treatment, the recurrence rate and mortality rate are still high. Clinicians should be alert to the possibility of this disease and achieve early detection and treatment.

BackgroundGastric cancer occupies the fourth highest morbidity rate of cancers worldwide. A higher incidence of gastric cancer had been found in East Asia compared to the other regions. Gastrectomy with radical lymph node dissection is the cornerstone of curative treatment for Stage III gastric cancer, and postoperative systemic chemotherapy with docetaxel, S-1 improved patients’ disease-free survival rates. However, advances in immunotherapy bring innovations in the management of patients with gastric cancer. The objective of this study was to explore the efficacy and safety of camrelizumab in combination with docetaxel + S-1, sequenced by camrelizumab + S-1 in stage III gastric cancer patients who are EBV positive, with defective mismatch repair and CPS ≥5.Methods and analysisThis prospective, open-label, single-arm trial was performed at Renji Hospital. In this study, a total of 70 adult patients aged 18–80 years with Stage III (PD-1+/MSI-H/EBV+/dMMR) gastric cancer confirmed by post-operative pathology will be enrolled after screening. Participants will receive the specific chemotherapy regimen until 1 year after the operation or until tumor recurrence or metastasis. The primary outcome is the 3-year disease-free survival rate measured by the Clopper-Pearson method and 95% confidence intervals. The secondary outcomes include overall survival, incidence and severity of adverse effects, and laboratory abnormalities. The data will be analyzed by the Kaplan-Meier method and log-rank test. The patients will be followed up every 3 months with imaging investigation until clinical remission.Ethics and disseminationAll participants will provide informed consent. The protocol has been approved by the Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (KY2019-191). The results will be disseminated through peer-reviewed manuscripts, reports and presentations.Clinical Trial RegistrationClinicalTrials.gov, identifier: ChiCTR1900027123. Registration date November 2019; first enrolment December 2019; expected end date December 2021; trial status: Ongoing.Brief AbstractA clinical trial for Stage III (PD-1+/MSI-H/EBV+/dMMR) gastric cancer patients who accepted anti-PD-1 therapy combined with docetaxel + S-1 as the first-line treatment and explored improvements in three-year disease-free survival rate.

ObjectivePrevious studies that have reported trends on abdominal obesity among US children were usually based on anthropometric assessments. However, little is known about the recent trends in central adiposity measures by DXA and abdominal obesity since 2011–2012.Study DesignA serial cross-sectional analysis of US population-weighted data among children from NHANES 2011 to 2018 was conducted.ResultsBetween 2011–2012 and 2017–2018, there was a relatively stable trend among children aged 8–19 years in trunk fat and trunk fat percentage. During the same time periods, there were no significant changes in prevalence of abdominal obesity by waist circumference (18.6 vs. 21.1%) among those aged 2–19 years, and abdominal obesity by WHtR (34.1 vs. 36.2%) among those aged 6–19 years. However, a significant increase trend among boys aged 2–19 years was found in prevalence of abdominal obesity by waist circumference (16.1–22.7%; P = 0.004). For Mexican American youth and non-Hispanic Asian boys, there is a significant increase in mean trunk fat percentage and waist circumference.ConclusionBetween 2011–2012 and 2017–2018, there have been no significant changes in central adiposity measured by DXA and prevalence of abdominal obesity among US children. Our study further supports that there is an urgent need to improve their lifestyle to reduce abdominal obesity for US children, especially for Mexican American youth and non-Hispanic Asian boys.

Mycoplasmas as economically important and pantropic pathogens can cause similar clinical diseases in different hosts by eluding host defense and establishing their niches despite their limited metabolic capacities. Besides, enormous undiscovered virulence has a fundamental role in the pathogenesis of pathogenic mycoplasmas. On the other hand, they are host-specific pathogens with some highly pathogenic members that can colonize a vast number of habitats. Reshuffling mycoplasmas genetic information and evolving rapidly is a way to avoid their host’s immune system. However, currently, only a few control measures exist against some mycoplasmosis which are far from satisfaction. This review aimed to provide an updated insight into the state of mycoplasmas as pathogens by summarizing and analyzing the comprehensive progress, current challenge, and future perspectives of mycoplasmas. It covers clinical implications of mycoplasmas in humans and domestic and wild animals, virulence-related factors, the process of gene transfer and its crucial prospects, the current application and future perspectives of nanotechnology for diagnosing and curing mycoplasmosis, Mycoplasma vaccination, and protective immunity. Several questions remain unanswered and are recommended to pay close attention to. The findings would be helpful to develop new strategies for basic and applied research on mycoplasmas and facilitate the control of mycoplasmosis for humans and various species of animals.

Although freezing is the most common and widespread way to preserve food for a long time, the accumulation of microstructural damage caused by ice crystal formation during freezing and recrystallization phenomena during thawing tends to degrade the quality of the product. Thus, the side effects of the above processes should be avoided as much as possible. To evaluate the effect of different magnetic field strength assisted thawing (MAT) on beef quality, the indicators associated with quality of MAT-treated (10–50 Gs) samples and samples thawed without an external magnetic field were compared. Results indicated that the thawing time was reduced by 21.5–40% after applying MAT. Meat quality results demonstrated that at appropriate magnetic field strengths thawing loss, TBARS values, cooking loss, and shear force were significantly decreased. Moreover, by protecting the microstructure of the muscle, MAT significantly increased the a∗ value and protein content. MAT treatment significantly improved the thawing efficiency and quality of frozen beef, indicating its promising application in frozen meat thawing.

PurposePost hemorrhagic shock mesenteric lymph (PHSML) return contributes to CD4+ T cell dysfunction, which leads to immune dysfunction and uncontrolled inflammatory response. Tumor necrosis factor α induced protein 8 like-2 (TIPE2) is one of the essential proteins to maintain the immune homeostasis. This study investigated the role of TIPE2 in regulation of CD4+ T lymphocyte function in interaction of PHSML and TLR2/TLR4.MethodsThe splenic CD4+ T cells were isolated from various mice (WT, TLR2-/-, TLR4-/-) by immunomagnetic beads, and stimulated with PHSML, normal lymphatic fluid (NML), respectively. Application of TIPE2-carrying interfering fragments of lentivirus were transfected to WT, TLR4-/-, and TLR2-/- CD4+ T cells, respectively. After interference of TIPE2, they were stimulated with PHSML and NML for the examinations of TIPE2, TLR2, and TLR4 mRNA expressions, proliferation, activation molecules on surface, and cytokine secretion function.ResultsPHSML stimulation significantly upregulated TIPE2, TLR2, and TLR4 mRNA expressions, decreased proliferation, CD25 expression, and IFN-γ secretion, and increased the secretion ability of IL-4 in WT CD4+ T cells. TIPE2 silencing enhanced proliferative capacity, upregulated CD25 expression, and increased IFNγ secretion in CD4+ T cells. PHSML stimulated TLR2-/-CD4+ T or TLR4-/-CD4+ T cells of which TIPE2 were silenced. TLR2 or TLR4 knockout attenuated PHSML-induced CD4+ T cells dysfunction; PHSML stimulation of silent TIPE2-expressing TLR2-/-CD4+ T or TLR4-/-CD4+ T revealed that the coexistence of low TIPE2 expression with lack of TLR2 or TLR4 eliminated this beneficial effect.ConclusionTIPE2 improves the PHSML-mediated CD4+T cells dysfunction by regulating TLR2/TLR4 pathway, providing a new intervention target following hemorrhagic shock-induced immune dysfunction.

On an organismal level, metabolism needs to react in a well-orchestrated manner to metabolic challenges such as nutrient uptake. Key metabolic hubs in human blood are pyruvate and lactate, both of which are constantly interconverted by very fast exchange fluxes. The quantitative contribution of different food sources to these metabolite pools remains unclear. Here, we applied in vivo stable isotope labeling to determine postprandial metabolic fluxes in response to two carbohydrate sources of different complexity. Depending on the ingested carbohydrate source, glucose or wheat flour, the net direction of the lactate dehydrogenase, and the alanine amino transferase fluxes were adjusted in a way to ensure sufficient availability, while, at the same time, preventing an overflow in the respective metabolite pools. The systemic lactate pool acts as a metabolic buffer which is fueled in the early- and depleted in the late-postprandial phase and thus plays a key role for systemic metabolic homeostasis.

ObjectiveWe sought to conduct a systematic review and meta-analysis of clinical adverse events in patients undergoing transcatheter aortic valve replacement (TAVR) with bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) anatomy and the efficacy of balloon-expandable (BE) vs. self-expanding (SE) valves in the BAV population. Comparisons aforementioned will be made stratified into early- and new-generation devices. Differences of prosthetic geometry on CT between patients with BAV and TAV were presented. In addition, BAV morphological presentations in included studies were summarized.MethodObservational studies and a randomized controlled trial of patients with BAV undergoing TAVR were included according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.ResultsA total of 43 studies were included in the final analysis. In patients undergoing TAVR, type 1 BAV was the most common phenotype and type 2 BAV accounted for the least. Significant higher risks of conversion to surgical aortic valve replacement (SAVR), the need of a second valve, a moderate or severe paravalvular leakage (PVL), device failure, acute kidney injury (AKI), and stroke were observed in patients with BAV than in patients with TAV during hospitalization. BAV had a higher risk of new permanent pacemaker implantation (PPI) both at hospitalization and a 30-day follow-up. Risk of 1-year mortality was significantly lower in patients with BAV than that with TAV [odds ratio (OR) = 0.85, 95% CI 0.75–0.97, p = 0.01]. BE transcatheter heart valves (THVs) had higher risks of annular rupture but a lower risk of the need of a second valve and a new PPI than SE THVs. Moreover, BE THV was less expanded and more elliptical in BAV than in TAV. In general, the rates of clinical adverse events were lower in new-generation THVs than in early-generation THVs in both BAV and TAV.ConclusionsDespite higher risks of conversion to SAVR, the need of a second valve, moderate or severe PVL, device failure, AKI, stroke, and new PPI, TAVR seems to be a viable option for selected patients with severe bicuspid aortic stenosis (AS), which demonstrated a potential benefit of 1-year survival, especially among lower surgical risk population using new-generation devices. Larger randomized studies are needed to guide patient selection and verified the durable performance of THVs in the BAV population.

BackgroundTo compare the efficacy and safety of pembrolizumab combined with neoadjuvant chemotherapy (neoCT) versus neoadjuvant chemoradiotherapy (neoCRT) followed by surgery for locally advanced resectable oesophageal squamous cell carcinoma (ESCC).MethodsThis study is a multicentre, prospective, randomized-controlled, phase III clinical study. Eligible ESCC (staging: cT1N2M0 or cT2-3N0-2M0 (stage II/III, high-risk lesions in T2N0M0)) patients will be randomly assigned to either the experimental group (pembrolizumab with neoCT, n = 228) or the control group (neoCRT, n = 114) at a ratio of 2:1. Within 4–6 weeks after preoperative therapy, the McKeown procedure will be performed. Patients in the experimental group will also receive pembrolizumab alone as adjuvant therapy after surgery until 1 year or until the radiographically confirmed PD or other condition indicated for premature termination is observed. The primary endpoint is event-free survival (EFS). The secondary endpoints are 1-, 3-, and 5-year overall survival (OS) and disease-free survival (DFS), short-term outcomes, and quality of life.DiscussionThis is the first prospectively randomized controlled trial designed to compare pembrolizumab plus chemotherapy and chemoradiotherapy as neoadjuvant therapy for resectable ESCC. According to our hypothesis, preoperative pembrolizumab combined with chemotherapy will result in a better tumour response and prolong the survival of patients, with acceptable toxicity. This study started in December 2021, and the enrolment time is estimated to be 2 years.Trial RegistrationThis prospective study has been registered at ClinicalTrials.gov (NCT04807673), March 2021.

Probiotics, prebiotics, and synbiotics can alleviate metabolic syndrome by altering the composition of the gut microbiota. Live combined Enterococcus faecium and Bacillus subtilis has been indicated to promote growth and reduce inflammation in animal models. However, the modulatory effects of live combined B. subtilis R-179 and E. faecium R-026 (LCBE) on human microbiota remain unclear. The current study examined the growth of these two strains in the presence of various oligosaccharides and assessed the effects of this probiotic mixture on human and murine gut microbiota in vitro and in vivo. Oligosaccharides improved the growth of E. faecium R-026 and B. subtilis R-179 as well as increased their production of short-chain fatty acids. E. faecium R-026 or B. subtilis R-179 co-incubated with Bifidobacterium and Clostridium significantly increased the number of the anaerobic bacteria Bifidobacterium longum and Clostridium butyricum by in vitro fermentation. Moreover, LCBE significantly reduced plasma cholesterol levels in mouse models of hyperlipidemia. LCBE combined with galacto-oligosaccharides led to a significant decrease in the Firmicutes/Bacteroidetes ratio and a significant increase in the relative abundance of Akkermansia and Bifidobacteria after treating mice with LCBE (0.23 g/day) for eight weeks. Furthermore, in vitro fermentation also showed that both the single strains and the two-strain mixture modulated human gut microbiota, resulting in increased Lactobacillus and Bifidobacteria, and decreased Escherichia-Shigella. Overall, these results suggest that LCBE can improve host health by reducing the level of cholesterol in mouse models by modifying the composition of the gut microbiota.

Optical feedback cavity ringdown spectroscopy is presented with a linear Fabry–Pérot cavity and a cost-effective DFB laser. To circumvent the low coupling efficiency caused by the broad laser linewidth, an optical feedback technique is used, and an enhanced coupling efficiency of 31%, mainly limited by impedance mismatch and mode mismatch, is obtained. The trigger of the ringdown event is realized by the shutoff of the laser driving current, and a novel method with the aid of one electronic switch is applied to avoid the ringdown events excited by the unexpected cavity modes during the process of laser current recovery. As a result, the ringdown signal with a signal-to-noise ratio of 2500 is achieved. Through continuous monitoring, the fractional uncertainty of the empty cavity ringdown times is assessed to be 0.04%. An Allan variance analysis indicates a detection sensitivity of 4.3 × 10−10 cm−1 is resulted at an integration time of 120 s, even with a moderate finesse cavity. To further improve the long-term stability, we regularly rectify the empty cavity ringdown time, and an improvement factor of 2.5 is demonstrated.