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Abstract Background Congenitally missing tooth is the most common dental abnormality which leaves spaces in the arch, leads to numerous forms of malocclusion due to the Bolton index discrepancy and is even associated with abnormal craniofacial morphology. Even though the roles of malocclusion and tooth loss in temporomandibular disorders (TMD) development remain controversial, basic researches have found some common molecules are involved in osteoarthritis and dental agenesis. However, the association of congenitally missing teeth with TMD is unknown. We hence investigated the association of congenitally missing teeth with TMD. Methods A cross-sectional analysis of 586 control participants (male: 287, female: 299, 38.33 ± 11.65 years) and 583 participants with non-third molar congenitally missing teeth (male: 238, female: 345, 39.13 ± 11.67 years) who consecutively received routine dental and TMD checkup according to Diagnostic Criteria for Temporomandibular Disorders Axis I in Health Management Center, Xiangya Hospital was performed. Logistic regression analysis was used to study the association of congenitally missing teeth with TMD. Results The congenitally missing teeth group included 581 hypodontia and 2 oligodontia participants. The congenitally missing anterior teeth participants, the congenitally missing posterior teeth participants and participants with both congenitally missing anterior and posterior teeth accounted for 88.34%, 8.40% and 3.26% of the congenitally missing teeth group respectively. Congenitally missing teeth group had greater ratios of females and orthodontic history. Participants with congenitally missing teeth had a significantly higher prevalence of overall TMD (67.24%) in comparison to control participants (45.90%). After adjusting age, gender, presence of congenitally missing teeth, number of congenitally missing teeth, number of non-congenitally missing teeth, number of dental quadrants with missing teeth, visible third molar and orthodontic history, the variables of age, gender, presence of congenitally missing teeth and number of dental quadrants with missing teeth were significant for overall TMD. Multivariable logistic regression analysis showed congenitally missing tooth was significantly related with overall TMD [odds ratio (OR):1.689(1.080–2.642), P = 0.022], intra-articular TMD [OR: 1.711(1.103–2.656), P = 0.017] and pain-related TMD [OR: 3.093(1.321–7.239), P = 0.009]. Conclusion Congenitally missing tooth is a risk factor for TMD. When treating the congenitally missing teeth population, TMJ evaluation and multidisciplinary strategies are necessary.

Ambient light interference stands as the primary source of noise encountered by the light detection and ranging (LiDAR) systems based on single-photon avalanche diode (SPAD), which seriously restricts the detection range and accuracy of sensors. Multi-event mode and time-gating method are extensively employed due to their effective suppression ability of the ambient light interference with easily implemented circuit structure. However, the current research on these two operational modes is limited to qualitative description, lacking a comprehensive theoretical analysis. This paper investigates the impact of the multi-event mode and time-gating method on enhancing the imaging capabilities of the sensor, employing a probability distribution perspective. A behavioral model is established, enabling the simulation of the comprehensive functionality of a SPAD-based LiDAR system in either first-hit mode or multi-event mode, including the histogramming, coincident detection, time- gating functions. The model can serve as a substitute for the actual circuit in system function validation and parameter optimization, thereby significantly reducing the design and simulation cycle.

BackgroundBloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) have received much attention. However, few studies have identified risk factors for CRKP BSIs in comparison to CRKP non-bloodstream infections (non-BSIs). This study aimed to compare the epidemiology, risk factors, and outcomes of CRKP BSIs and CRKP non-BSIs.MethodsWe conducted a retrospective study of patients infected with CRKP in the ICU from January 2012 to December 2020. Clinical characteristics and outcomes were compared between CRKP BSIs and CRKP non-BSIs. Predictors associated with 28-day all-cause mortality in CRKP-infected patients were also evaluated.Results326 patients infected with CRKP were enrolled, including 96 patients with CRKP BSIs and 230 with CRKP non-BSIs. The rates of CRKP BSIs in CRKP infections were generally raised from 2012 (12.50%) to 2020 (45.76%). Multivariate logistic analysis indicated that the use of carbapenems within the prior 90 days was an independent risk factor for CRKP BSIs (p = 0.019). Compared to CRKP non-BSIs, CRKP isolates in the CRKP BSI group were found to be non-susceptible to more tested carbapenems (p = 0.001). Moreover, the CRKP BSI group exhibited a higher mortality rate (p = 0.036). The non-susceptibility of CRKP isolates to more tested carbapenems (p = 0.025), a high SOFA score (p = 0.000), and the use of antifungal drugs within the prior 90 days (p = 0.018) were significant factors for 28-day all-cause mortality in CRKP-infected patients.ConclusionThe proportion of CRKP BSI increased progressively in CRKP-infected patients over 9 years. The use of carbapenems within the prior 90 days was an independent risk factor for the development of CRKP BSIs. The non-susceptibility of CRKP isolates to more tested carbapenems and a higher mortality rate were found in the CRKP BSI group.

The replacement of plastic film with biodegradable film is important for reducing plastic film residual pollution in semi-arid regions of northern China. However, information on biodegradable film improvements based on the hydrothermal requirements of major food crops in the typical plastic film mulching area is limited. This study used a combination of field data measurements and curve fitting to assess the spatiotemporal distribution of soil hydrothermal variation and the corresponding maize yield in the field under biodegradable film mulching (BM), polyethylene film mulching (PM), and without mulching (CT). The warming effect of BM was between those of PM and CT and all treatments differed significantly from each other. The duration of the warming effect of BM was shorter than that of PM, and the warming effect of both disappeared at the early jointing stage of maize. The BM soil moisture was significantly lower compared with PM and CT throughout the soil profile (0–180 cm). Moreover, moisture fluctuations were observed in the 0–40 and 40–120 cm soil layers of BM after degradation, and the timing of fluctuations coincided with the filling period of maize. Consequently, the water use efficiency and yield of BM were lower than those of PM. Hence, we suggest that the conservation effect of biodegradable film mulching on soil moisture should persist until the end of the maize filling period, and that the start-up stage of degradation cannot be based solely on the disappearance of the warming effect.

Abstract Ovarian reserve (OR) and fertility are critical in women's healthcare. Clinical methods for encoding OR and fertility rely on the combination of tests, which cannot serve as a multi‐functional platform with limited information from specific biofluids. Herein, metabolic fingerprinting of follicular fluid (MFFF) from follicles is performed, using particle‐assisted laser desorption/ionization mass spectrometry (PALDI‐MS) to encode OR and fertility. PALDI‐MS allows efficient MFFF, showing fast speed (≈30 s), high sensitivity (≈60 fmol), and desirable reproducibility (coefficients of variation

Neuro-navigation is a key technology to ensure the clinical efficacy of TMS. However, the neuro-navigation system based on positioning sensor is currently unable to be promoted and applied in clinical practice due to its time-consuming and high-cost. In the present study, we designed I-Helmet system to promote an individualized and clinically friendly neuro-navigation approach to TMS clinical application. I-Helmet system is based on C++ with a graphical user interface that allows users to design a 3D-printed helmet model for coil navigation. Besides, a dedicated coil positioning accuracy detection method was promoted based on three-dimensional (3D) printing and 3D laser scanning for evaluation. T1 images were collected from 24 subjects, and based on each image, phantom were created to simulate skin and hair. Six 3D-printed helmets with the head positioning hole enlarged by 0–5% tolerance in 1% increments were designed to evaluate the influences of skin, hair, and helmet-tolerance on the positioning accuracy and contact force of I-Helmet. Finally, I-Helmet system was evaluated by comparing its positioning accuracy with three skin hardnesses, three hair styles, three operators, and with or without landmarks. The accuracy of the proposed coil positioning accuracy detection method was about 0.30 mm in position and 0.22° in orientation. Skin and hair had significant influences on positioning accuracy (p 0.05). The tolerance of the helmet presented significant influences on positioning accuracy (p

Background and objectiveIt has been proved that repetitive transcranial magnetic stimulation (rTMS) triggers the modulation of homeostatic metaplasticity, which causes the effect of rTMS to disappear or even reverse, and a certain length of interval between rTMS trains might break the modulation of homeostatic metaplasticity. However, it remains unknown whether the effects of high-frequency rTMS can be modulated by homeostatic metaplasticity by lengthening the train duration and whether homeostatic metaplasticity can be broken by prolonging the inter-train interval.MethodsIn this study, 15 subjects participated in two experiments including different rTMS protocols targeting the motor cortex. In the first experiment, high-frequency rTMS protocols with different train durations (2 s and 5 s) and an inter-train interval of 25 s were adopted. In the second experiment, high-frequency rTMS protocols with a train duration of 5 s and different inter-train intervals (50 s and 100 s) were adopted. A sham protocol was also included. Changes of motor evoked potential amplitude acquired from electromyography, power spectral density, and intra-region and inter-region functional connectivity acquired from electroencephalography in the resting state before and after each rTMS protocol were evaluated.ResultsHigh-frequency rTMS with 2 s train duration and 25 s inter-train interval increased cortex excitability and the power spectral density of bilateral central regions in the alpha frequency band and enhanced the functional connectivity between central regions and other brain regions. When the train duration was prolonged to 5 s, the after-effects of high-frequency rTMS disappeared. The after-effects of rTMS with 5 s train duration and 100 s inter-train interval were the same as those of rTMS with 2 s train duration and 25 s inter-train interval.ConclusionOur results indicated that train duration and inter-train interval could induce the homeostatic metaplasticiy and determine the direction of intensity of rTMS after-effects, and should certainly be taken into account when performing rTMS in both research and clinical practice.

Background At present, the avoidance of drug shortages mainly relies on expert experience. This study aimed to establish an evaluation index system for the risk of drug shortages in medical institutions in China and to apply the system to guide the graded management of drugs in short supply.Methods A two-round Delphi process was conducted to determine the indicators in the index system. The weight value of each indicator was calculated using analytic hierarchy process (AHP) methods. The data of drugs in short supply from January 1 to December 31, 2020 in Hunan province were collected and evaluated using this index system. The evaluation scores, which ranged from 0 to 100, were calculated.Results A three-level index system with four first-level indicators, 11 second-level indicators, and 36 third-level indicators was constructed by the two rounds of the Delphi process. The expert authority coefficient (Cr) of the first and second rounds of consultation were 0.88 and 0.90, respectively. The Kendall’s coefficients of concordance (Kendall’s W) for the two rounds of consultation were 0.44 and 0.50, respectively (P < .05). For the first-level indicators ‘supply stability,’ ‘causes of shortage,’ ‘medicine availability in medical institution’ and ‘pharmaceutical properties,’ the weight values were 0.3253, 0.2489, 0.2398, and 0.1860, respectively. Based on the risk evaluation score, drugs (dosage strength) at high risk of shortage included sodium thiosulfate (0.64 g), posterior pituitary lobe hormones (1 mL:6 IU), protamine sulfate (5 mL:50 mg), thrombin (500 U), urokinase (10 WU), and rotundine sulfate (2 mL:60 mg).Conclusion An indexed system for the risk assessment of drug shortages in China was established to guide the graded response to drug shortages in medical institutions and the implementation of differential management strategies to address these shortages.

Understanding of orchard nutrition status can facilitate the proper management of orchards for higher fruit yield and quality. From 2011 to 2019, the nutrition status of orchards in Hunan Province, a major citrus-producing area in china, were assessed. A total of 361 soil samples, 378 leaf samples and 285 fruit samples of sweet oranges including navel orange (citrus sinensis l. Osbeck ‘newhall’) and common sweet orange (citrus sinensis l. Osbeck ‘bingtangcheng’), and mandarins including satsuma mandarin (citrus unshiu marc. ‘miyagawa’) and ponkan (citrus reticulata blanco ‘xinnu’) were collected. These samples were from112 sweet orange orchards and 140 mandarin orchards. Parameters of soil, leaf and fruit nutrition and fruit quality were analyzed based on these samples. The results revealed that soil acidification occurred in 79.0% of sweet orange orchards (ph 3.56 to 8.12) and 74.7% of mandarin orchards (ph 2.75 to 8.15). Soil organic matter (om) was abundant in both sweet orange orchards (21.3 g/kg on average) and mandarin orchards (19.77 g/kg on average). Nutrient analysis demonstrated deficiencies of nitrogen (n), potassium (k) and boron (b) in soils and leaves of sweet orange and mandarin orchards. Zinc (zn) was abundant in soils but deficient in leaves, suggesting a low zn utilization efficiency in these orchards. Besides, excessive iron (fe), magnesium (mn) and copper (cu) were found in sweet orange and mandarin leaves, which may be associated with low soil ph and fungicides application in this area. The average contents of n, phosphorus (p) and k in the fruit were about 0.80%, 0.11% and 0.51%, respectively, with a ratio close to 1:0.14:0.6. Multiple linear regression (mlr) analysis revealed that leaf npk and molybdenum (mo) significantly affect fruit fresh fruit weight (ffw) and total soluble solids (tss), and leaf p is closely correlated with fruit titratable acid (ta).

Background In 2019, the National Health Commission issued the Capacity Standards for Community Health Service Center (2018 version), which proposed that the 56 common disease species should be offered diagnosis and treatment services by CHSC, but it did not specify the common disease species of children in the community, which to some extent affects the assessment and construction of CHSC capacity in the community. Objective To investigate and analyze the common childhood disease species and their characteristics in community health services, in order to provide a reference basis for further community child health service capacity building. Methods In April 2020, a convenience sampling method was adopted to select community health service agencies in 11 different level cities in China as the sample unit. A self-designed questionnaire was administered to cover the subject's basic condition, the common childhood disease conditions suitable for diagnosis and treatment in the community, and their sequencing. Filled out online voluntarily anonymously by child health service personnel at the sample institution, 3 090 cases were successfully investigated. Respondents ranked the common degree of children's related disorders from low to high, assigning 1 to 5 points to each of the top 5 common childhood disorders, which is, assigning 5 points to ranked 1, 1 point to ranked 5, and 0 points to unselected, calculating a total and sorting by total score. Results The top 5 disease categories for children in the community were acute upper respiratory infection, diarrhea, bronchitis, pneumonia, and eczema. Of the top 10 ranked community common childhood disorders, 3 were respiratory, 3 were facial and dermatologic, 2 were infectious, and 1 each was a digestive and growth and development related disorder. The top 5 common childhood diseases ranked by different regions, different levels of cities and different posts were consistent, but the ranking order was different, but there were differences in the 6th-10th disease species and order. Conclusion The current coverage of common childhood diseases in community health services is high. There is regional, urban, and post heterogeneity in common childhood disease species in communities. Construction of community child health service capacity should be oriented to improve the capacity of diagnosis and treatment service of common childhood diseases in the community, and fully consider the disease species variability in different regions, cities, and posts.

Abstract Background Pulmonary hypertension (PH) is a progressive and fatal cardiopulmonary disease characterized by pulmonary vascular remodeling and increased pulmonary vascular resistance and artery pressure. Vascular remodeling is associated with the excessive cell proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). In this paper, the effects of heat shock protein-110 (HSP110) on PH were investigated. Methods The C57BL/6 mice and human PASMCs (HPASMCs) were respectively exposed to hypoxia to establish and simulate PH model in vivo and cell experiment in vitro. To HSP110 knockdown, the hypoxia mice and HPASMCs were infected with adeno-associated virus or adenovirus carring the shRNAs (short hairpin RNAs) for HSP110 (shHSP110). For HSP110 and yes-associated protein (YAP) overexpression, HPASMCs were infected with adenovirus vector carring the cDNA of HSP110 or YAP. The effects of HSP110 on PH development in mice and cell proliferation, migration and autophagy of PASMCs under hypoxia were assessed. Moreover, the regulatory mechanisms among HSP110, YAP and TEA domain transcription factor 4 (TEAD4) were investigated. Results We demonstrated that expression of HSP110 was significantly increased in the pulmonary arteries of mice and HPASMCs under hypoxia. Moreover, knockdown of HSP110 alleviated hypoxia-induced right ventricle systolic pressure, vascular wall thickening, right ventricular hypertrophy, autophagy and proliferation of PASMCs in mice. In addition, knockdown of HSP110 inhibited the increases of proliferation, migration and autophagy of HPASMCs that induced by hypoxia in vitro. Mechanistically, HSP110 knockdown inhibited YAP and transcriptional co-activator with PDZ-binding motif (TAZ) activity and TEAD4 nuclear expression under hypoxia. However, overexpression of HSP110 exhibited the opposite results in HPASMCs. Additionally, overexpression of YAP partially restored the effects of shHSP110 on HPASMCs. The interaction of HSP110 and YAP was verified. Moreover, TEAD4 could promote the transcriptional activity of HSP110 by binding to the HSP110 promoter under hypoxia. Conclusions Our findings suggest that HSP110 might contribute to the development of PH by regulating the proliferation, migration and autophagy of PASMCs through YAP/TAZ-TEAD4 pathway, which may help to understand deeper the pathogenic mechanism in PH development.

Abstract Background The doctor/nurse and police officer population have some common typical characteristics of great professional pressure and night shift and past studies indicated oral mucosa lesions were closely associated with psychological factors and health-risking behaviors, however the prevalence of recurrent aphthous stomatitis (RAS) and the two commonly seen oral potentially malignant disorders of oral submucosal fibrosis (OSF) and oral leukoplakia in doctor/nurse and police officer in the Betel quid chewing city of Mainland China is unknown The cross-sectional study was to determine the prevalence differences of RAS, oral leukoplakia and OSF among doctor/nurse, police officer and non-doctor/nurse and non-police officer population aged 20–59 years. Methods RAS, OSF and oral leukoplakia were examined in doctor/nurse group (male: 659, female: 2439), police officer group (male: 839, female: 262) and non-doctor/nurse and non-police officer group (male: 7576, female: 8129) from 2020-11-01 to 2021-08-31 in Health Management Center, Xiangya Hospital in Changsha city, Hunan province. Results The prevalence rates of RAS, OSF, oral leukoplakia and oral leukoplakia combined with OSF in male and female non-doctor/nurse and non-police officer group are 8.32‰ and 10.83‰, 58.08‰ and 1.23‰, 11.75‰ and 0.25‰, 7.66‰ and 0.12‰ respectively. Compared with the non-doctor/nurse and non-police officer population, prevalence rates of RAS in male (24.27‰) and female (20.50‰) doctor/nurse population were significantly higher. Prevalence rates of OSF (21.24‰) and oral leukoplakia (3.03‰) in male doctor/nurse population were significantly less but prevalence rates of OSF (93.71‰), oral leukoplakia (20.17‰) and oral leukoplakia combined with OSF (15.42‰) for male police officer were significantly greater in comparison with male non-doctor/nurse and non-police officer group. OSF and oral leukoplakia prevalence rates were obvious lower for the female than the counterpart male group, but there were no significant differences of OSF and oral leukoplakia prevalence rates between the female non-doctor/nurse and non-police officer and female doctor/nurse group. Oral leukoplakia was not found in the female police officers. Conclusions Doctor/nurse population have higher prevalence of RAS. Male doctors/nurses have lower prevalence of OSF and oral leukoplakia, while male police officers have higher prevalence of OSF, oral leukoplakia and oral leukoplakia combined with OSF.

In this work, we have successfully fabricated Sr-doped porous LaFeO3 samples via sol–gel method. The results reveal that Sr2+ cation is effectively doped into LaFeO3 crystal lattice substituting La3+ cation. The visible light catalytic performance of the materials was evaluated by the degradation of 2,4-dichlorophenol (2,4-DCP) and Rhodamine B (RhB). The amount-optimized Sr-doped porous LaFeO3 sample exhibited outstanding visible-light catalytic performance for the degradation of the model pollutants compared to the porous LaFeO3 alone. The enhanced performance was accredited to the enlarged surface area, absorption extension via the surface states of the introduced Sr2+ below the conduction band bottom of LaFeO3, and promoted charge carrier’s separation as confirmed by various experiments. Experiments of radical trapping reveal that •OH species are dominant intermediate oxidants involved in the oxidation of 2,4-DCP and RhB over the optimized sample. This research will provide new routes for environmental remediation based on the LaFeO3 semiconductor.

Objectives Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection/colonisation has been reported in hospitals. The clinical characteristics of CRKP infection/colonisation in the intensive care unit (ICU) have received little attention. This study aims to investigate the epidemiology and extent of K. pneumoniae (KP) resistance to carbapenems, the sources of CRKP patients and CRKP isolates, and the risk factors for CRKP infection/colonisation.Design Retrospective single-centre study.Data source Clinical data were obtained from electronic medical records.Participants Patients isolated with KP in the ICU from January 2012 to December 2020.Main outcome measures The prevalence and changing trend of CRKP were determined. The extent of KP isolates resistance to carbapenems, the specimen types of KP isolates, and the sources of CRKP patients and CRKP isolates were all examined. The risk factors for CRKP infection/colonisation were also assessed.Results The rate of CRKP in KP isolates raised from 11.11% in 2012 to 48.92% in 2020. CRKP isolates were detected in one site in 266 patients (70.56%). The percentage of CRKP isolates not susceptible to imipenem increased from 42.86% in 2012 to 98.53% in 2020. The percentage of CRKP patients from general wards in our hospital and other hospitals gradually converged in 2020 (47.06% vs 52.94%). CRKP isolates were mainly acquired in our ICU (59.68%). Younger age (p=0.018), previous admission (p=0.018), previous ICU stay (p=0.008), prior use of surgical drainage (p=0.012) and gastric tube (p=0.001), and use of carbapenems (p=0.000), tigecycline (p=0.005), β-lactams/β-lactamase inhibitors (p=0.000), fluoroquinolones (p=0.033), and antifungal drugs (p=0.011) within the prior 3 months were independent risk factors for CRKP infection/colonisation.Conclusions Overall, the rate of KP isolates resistance to carbapenems increased, and the severity of this resistance significantly increased. Intensive and local infection/colonisation control measures are necessary for ICU patients, especially those with risk factors for CRKP infection/colonisation.

BackgroundHashimoto’s thyroiditis (HT) is a chronic autoimmune disease that poses a risk factor for papillary thyroid carcinoma (PTC). The present study aimed to identify the key genes shared by HT and PTC for advancing the current understanding of their shared pathogenesis and molecular mechanisms.MethodsHT- and PTC-related datasets (GSE138198 and GSE33630, respectively) were retrieved from the Gene Expression Omnibus (GEO) database. Genes significantly related to the PTC phenotype were identified using weighted gene co-expression network analysis (WGCNA). Differentially expressed genes (DEGs) were identified between PTC and healthy samples from GSE33630, and between HT and normal samples from GSE138198. Subsequently, functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Transcription factors and miRNAs regulating the common genes in PTC and HT were forecasted using the Harmonizome and miRWalk databases, respectively, and drugs targeting these genes were investigated using the Drug-Gene Interaction Database (DGIdb). The key genes in both GSE138198 and GSE33630 were further identified via Receiver Operating Characteristic (ROC) analysis. The expression of key genes was verified in external validation set and clinical samples using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).ResultsIn total, 690 and 1945 DEGs were associated with PTC and HT, respectively; of these, 56 were shared and exhibited excellent predictive accuracy in the GSE138198 and GSE33630 cohorts. Notably, four genes, Alcohol Dehydrogenase 1B (ADH1B), Active BCR-related (ABR), alpha-1 antitrypsin (SERPINA1), and lysophosphatidic acid receptor 5 (LPAR5) were recognized as key genes shared by HT and PTC. Subsequently, EGR1 was identified as a common transcription factor regulating ABR, SERPINA1, and LPAR5 expression. These findings were confirmed using qRT-PCR and immunohistochemical analysis.ConclusionFour (ADH1B, ABR, SERPINA1, and LPAR5) out of 56 common genes exhibited diagnostic potential in HT and PTC. Notably, this study, for the first time, defined the close relationship between ABR and HT/PTC progression. Overall, this study provides a basis for understanding the shared pathogenesis and underlying molecular mechanisms of HT and PTC, which might help improve patient diagnosis and prognosis.

BackgroundAnoikis is a programmed cell death process that was proven to be associated with cancer. Uroepithelial carcinoma of the bladder (BLCA) is a malignant disease of the urinary tract and has a strong metastatic potential. To determine whether anoikis-associated genes can predict the prognosis of BLCA accurately, we evaluated the prognostic value of anoikis-associated genes in BLCA and constructed the best model to predict prognosis.MethodThe BLCA transcriptome data were downloaded from TCGA and GEO databases, and genes with differential expression were selected and then clustered using non-negative matrix factorization (NMF). The genes with the most correlation with anoikis were screened and identified using univariate Cox regression, lasso regression, and multivariate Cox regression. The GEO dataset was used for external validation. Nomograms were created based on risk characteristics in combination with clinical variants and the performance of the model was validated with receiver operating characteristic (ROC) curves. The immunotherapeutic significance of this risk score was assessed using the immune phenomenon score (IPS). IC50 values of predictive chemotherapeutic agents were calculated. Finally, we used RT-qPCR to determine the mRNA expression of four genes, CALR, FASN, CASP6, and RAD9A.ResultWe screened 406 tumor samples and 19 normal tissue samples from the TCGA database. Based on anoikis-associated genes, we classified patients into two subtypes (C1 and C2) using NMF method. Subsequently, nine core genes were screened by multiple methods after analysis, which were used to construct risk profiles. The design of nomograms based on risk profiles and clinical variables, ROC, and calibration curves confirmed that the model could well have the ability to predict the survival of BLCA patients at 1, 3, and 5 years. By predicting the IC50 values of chemotherapeutic drugs, it was learned that the high-risk group (HRG) was more susceptible to paclitaxel, gemcitabine, and cisplatin, and the low-risk group (LRG) was more susceptible to veriparib and afatinib.ConclusionIn summary, the risk score of anoikis-associated genes can be applied as a predictor to predict the prognosis of BLCA in clinical practice.

Abstract Pancreatic ductal adenocarcinomas (PDAC) is one of the stiffest malignancies with strong solid stresses. Increasing stiffness could alter cellular behavior and trigger internal signaling pathways and is strongly associated with a poor prognosis in PDAC. So far, there has been no report on of an experimental model that can rapidly construct and stably maintain a stiffness gradient dimension in both vitro and in vivo. In this study, a gelatin methacryloyl (GelMA)‐based hydrogel was designed for in vitro and in vivo PDAC experiments. The GelMA‐based hydrogel has porous, adjustable mechanical properties and excellent in vitro and in vivo biocompatibility. The GelMA‐based in vitro 3D culture method can effectively form a gradient and stable extracellular matrix stiffness, affecting cell morphology, cytoskeleton remodeling, and malignant biological behaviors such as proliferation and metastasis. This model is suitable for in vivo studies with long‐term maintenance of matrix stiffness and no significant toxicity. High matrix stiffness can significantly promote PDAC progression and tumor immunosuppression. This novel adaptive extracellular matrix rigidity tumor model is an excellent candidate for further development as an in vitro and in vivo biomechanical study model of PDAC or other tumors with strong solid stresses.

BackgroundNeuroimaging studies have identified aberrant activity patterns in multiple brain regions in functional dyspepsia (FD) patients. However, due to the differences in study design, these previous findings are inconsistent, and the underlying neuropathological characteristics of FD remain unclear.MethodsEight databases were systematically searched for literature from inception to October 2022 with the keywords “Functional dyspepsia” and “Neuroimaging.” Thereafter, the anisotropic effect size signed the differential mapping (AES-SDM) approach that was applied to meta-analyze the aberrant brain activity pattern of FD patients.ResultsA total of 11 articles with 260 FD patients and 202 healthy controls (HCs) were included. The AES-SDM meta-analysis demonstrated that FD patients manifested increased activity in the bilateral insula, left anterior cingulate gyrus, bilateral thalamus, right precentral gyrus, left supplementary motor area, right putamen, and left rectus gyrus and decreased functional activity in the right cerebellum compared to the HCs. Sensitivity analysis showed that all these above regions were highly reproducible, and no significant publication bias was detected.ConclusionThe current study demonstrated that FD patients had significantly abnormal activity patterns in several brain regions involved in visceral sensation perception, pain modulation, and emotion regulation, which provided an integrated insight into the neuropathological characteristics of FD.

IntroductionTraditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations.Materials and methodsFunctional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted.ResultsIn comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC).ConclusionThese findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation’s effect.Clinical trial registrationClinicalTrials.gov, identifier, ChiCTR2100051893.

Abstract Background Computed tomography (CT)-guided cutting needle biopsy (CNB) is an effective diagnostic method for lung nodules (LNs). The false-negative rate of CT-guided lung biopsy is reported to be up to 16%. This study aimed to determine the predictors of true-negative results in LNs with CNB-based benign results. Methods From January 2011 to December 2015, 96 patients with CNB-based nonspecific benign results were included in this study as the training group to detect predictors of true-negative results. From January 2016 to December 2018, an additional 57 patients were included as a validation group to test the reliability of the predictors. Results In the training group, a total of 96 patients underwent CT-guided CNB for 96 LNs. The CNB-based results were true negatives for 82 LNs and false negatives for 14 LNs. The negative predictive value of the CNB-based benign results was 85.4% (82/96). Univariate and multivariate logistic regression analyses revealed that CNB-based granulomatous inflammation (P = 0.013, hazard ratio = 0.110, 95% confidential interval = 0.019–0.625) was the independent predictor of true-negative results. The area under the receiver operator characteristic (ROC) curve was 0.697 (P = 0.019). In the validation group, biopsy results for 47 patients were true negative, and 10 were false negative. When the predictor was used on the validation group, the area under the ROC curve was 0.759 (P = 0.011). Conclusions Most of the CNB-based benign results were true negatives, and CNB-based granulomatous inflammation could be considered a predictor of true-negative results.

Abstract Background Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, with a high prevalence and significant influence on the quality of life (QoL). Either acupuncture or moxibustion is effective for dyspepsia, which is confirmed by both ancient documents and modern research. However, the therapeutic advantage and underlying mechanism between acupuncture and moxibustion for FD remain unclear. Methods This randomized controlled fMRI trial aims to (i) evaluate the therapeutic advantages of acupuncture and moxibustion treatment for FD, (ii) investigate the similarities and differences in cerebral activity elicited by acupuncture and moxibustion, and (iii) analyze the possible correlations between brain responses and clinical variables thus to explore the potential central mechanism of acupuncture and moxibustion for treating FD. Ninety-two FD patients will be randomly assigned to either the acupuncture group or the moxibustion group in a 1:1 ratio. Twenty sessions of acupuncture or moxibustion treatment over 4 weeks will be performed on each patient. The short form Leeds Dyspepsia Questionnaire, the Nepean Dyspepsia Index, etc., are used to evaluate the therapeutic effects. The heart rate variability will be analyzed to investigate the autonomic nerve function. Thirty-six FD patients in each group will be randomly selected for the fMRI scan to detect cerebral activity changes. Discussion We expect the results will deepen our knowledge on the clinical value and underlying mechanism of acupuncture and moxibustion and provide a reference for a better selection of interventions for treating FD. Trial registration Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2100049496. Registered on 2 August 2021

Abstract Background Lots of studies have measured motor evoked potential (MEP) induced by transcranial magnetic stimulation (TMS) in anesthetized animals. However, in awake animals, the measurement of TMS-induced MEP is scarce as lack of sufficient restraint. So far, the explicit study of anesthesia effects on corticospinal excitability and repetitive TMS (rTMS) induced modulation is still lacking. This study aimed to: (1) measure TMS-induced MEP in both awake restrained and anesthetized rats, (2) investigate the effect of anesthesia on corticospinal excitability, and (3) on rTMS-induced modulation. Methods MEP of eighteen rats were measured under both wakefulness and anesthesia using flexible binding and surface electrodes. Peak-to-peak MEP amplitudes, resting motor threshold (RMT) and the slope of stimulus response (SR) were extracted to investigate anesthesia effects on corticospinal excitability. Thereafter, 5 or 10 Hz rTMS was applied with 600 pulses, and the increase in MEP amplitude and the decrease in RMT were used to quantify rTMS-induced modulation. Results The RMT in the awake condition was 44.6 ± 1.2% maximum output (MO), the peak-to-peak MEP amplitude was 404.6 ± 48.8 μV at 60% MO. Under anesthesia, higher RMT (55.6 ± 2.9% MO), lower peak-to-peak MEP amplitudes (258.6 ± 32.7 μV) and lower slope of SR indicated that the corticospinal excitability was suppressed. Moreover, under anesthesia, high-frequency rTMS still showed significant modulation of corticospinal excitability, but the modulation of MEP peak-to-peak amplitudes was weaker than that under wakefulness. Conclusions This study measured TMS-induced MEP in both awake and anesthetized rats, and provided explicit evidence for the inhibitory effects of anesthesia on corticospinal excitability and on high-frequency rTMS-induced modulation of MEP.

Background: Acupuncture reinforcing-reducing manipulation (ARRM) is a necessary procedure of traditional Chinese acupuncture and an essential factor affecting the therapeutic effect of acupuncture. Shaoshanhuo reinforcing method (SSH) and Toutianliang reducing method (TTL) are the most representative ARRMs. They integrate six single ARRMs and pose distinguished therapeutic effects of acupuncture. However, due to the complexity, diversity, and variation, investigating the mechanism of these two classic manipulations is insufficient. The neuroimaging technique is an important method to explore the central mechanism of SSH and TTL. This study attempted to design a randomized crossover trial based on functional near-infrared spectroscopy (fNIRS) to explore the mechanism of SSH and TTL, meanwhile, provide valuable methodological references for future studies.Methods: A total of 30 healthy subjects were finally included and analyzed in this study. fNIRS examination was performed to record the neural responses during the two most representative ARRMs. The cortical activation and the inter-network functional connectivity (FC) were explored.Results: The results found that SSH and TTL could elicit significant cerebral responses, respectively, but there was no difference between them.Conclusion: Neuroimaging techniques with a higher spatiotemporal resolution, combinations of therapeutic effects, and strict quality control are important to neuroimaging studies on SSH and TTL.

The neuropathological features of Alzheimer’s disease include amyloid plaques. Rapidly emerging evidence suggests that Piezo1, a mechanosensitive cation channel, plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure, but the importance of Piezo1-mediated mechanotransduction in brain functions is less appreciated. However, apart from mechanical stimulation, Piezo1 channels are strongly modulated by voltage. We assume that Piezo1 may play a role in converting mechanical and electrical signals, which could induce the phagocytosis and degradation of Aβ, and the combined effect of mechanical and electrical stimulation is superior to single mechanical stimulation. Hence, we design a transcranial magneto-acoustic stimulation (TMAS) system, based on transcranial ultrasound stimulation (TUS) within a magnetic field that combines a magneto-acoustic coupling effect electric field and the mechanical force of ultrasound, and applied it to test the above hypothesis in 5xFAD mice. Behavioral tests, in vivo electrophysiological recordings, Golgi–Cox staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, real-time quantitative PCR, Western blotting, RNA sequencing, and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1. TMAS treatment enhanced autophagy to promote the phagocytosis and degradation of β-amyloid through the activation of microglial Piezo1 and alleviated neuroinflammation, synaptic plasticity impairment, and neural oscillation abnormalities in 5xFAD mice, showing a stronger effect than ultrasound. However, inhibition of Piezo1 with an antagonist, GsMTx-4, prevented these beneficial effects of TMAS. This research indicates that Piezo1 can transform TMAS-related mechanical and electrical stimuli into biochemical signals and identifies that the favorable effects of TMAS on synaptic plasticity in 5xFAD mice are mediated by Piezo1.