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Abstract The current research of sandwich structures under dynamic loading mainly focus on the response characteristic of structure. The micro-topology of core layers would sufficiently influence the property of sandwich structure. However, the micro deformation and topology mechanism of structural deformation and energy absorption are unclear. In this paper, based on the bi-directional evolutionary structural optimization method and periodic base cell (PBC) technology, a topology optimization frame work is proposed to optimize the core layer of sandwich beams. The objective of the present optimization problem is to maximize shear stiffness of PBC with a volume constraint. The effects of the volume fraction, filter radius, and initial PBC aspect ratio on the micro-topology of the core were discussed. The dynamic response process, core compression, and energy absorption capacity of the sandwich beams under blast impact loading were analyzed by the finite element method. The results demonstrated that the over-pressure action stage was coupled with the core compression stage. Under the same loading and mass per unit area, the sandwich beam with a 20% volume fraction core layer had the best blast resistance. The filter radius has a slight effect on the shear stiffness and blast resistances of the sandwich beams. But increasing the filter radius could slightly improve the bending stiffness. Upon changing the initial PBC aspect ratio, there are three ways for PBC evolution: The first is to change the angle between the adjacent bars, the second is to further form holes in the bars, and the third is to combine the first two ways. However, not all three ways can improve the energy absorption capacity of the structure. Changing the aspect ratio of the PBC arbitrarily may lead to worse results. More studies are necessary for further detailed optimization. This research proposes a new topology sandwich beam structure by micro-topology optimization, which has sufficient shear stiffness. The micro mechanism of structural energy absorption is clarified, it is significant for structural energy absorption design.

Abstract Background Residual symptoms of depressive disorders are serious health problems. However, the progression process is hardly predictable due to high heterogeneity of the disease. This study aims to: (1) classify the patterns of changes in residual symptoms based on homogeneous data, and (2) identify potential predictors for these patterns. Methods In this study, we conducted a data-driven Latent Class Growth Analysis (LCGA) to identify distinct tendencies of changes in residual symptoms, which were longitudinally quantified using the QIDS-SR16 at baseline and 1/3/6 months post-baseline for depressed patients. The association between baseline characteristics (e.g. clinical features and cognitive functions) and different progression tendencies were also identified. Results The tendency of changes in residual symptoms was categorized into four classes: “light residual symptom decline (15.4%)”, “residual symptom disappears (39.3%)”, “steady residual symptom (6.3%)” and “severe residual symptom decline (39.0%)”. We observed that the second class displayed more favorable recuperation outcomes than the rest of patients. The severity, recurrence, polypharmacy, and medication adherence of symptoms are intricately linked to the duration of residual symptoms’ persistence. Additionally, clinical characteristics including sleep disturbances, depressive moods, alterations in appetite or weight, and difficulties with concentration have been identified as significant factors in the recovery process. Conclusions Our research findings indicate that certain clinical characteristics in patients with depressive disorders are associated with poor recovery from residual symptoms following acute treatment. This revelation holds significant value in the targeted attention to specific patients and the development of early intervention strategies for residual symptoms accordingly.

Background: Clearance of human papillomavirus (HPV) among adolescent men who have sex with men (MSM) is not well studied. This study aimed to evaluate the clearance of HPV DNA and antibodies among adolescent MSM. Methods: In our cohort study, we enrolled adolescent MSM in Melbourne between October 2010 and September 2013. At baseline, 3, 6, and 12 months, anal and penile swabs for HPV DNA and serum for HPV antibodies against genotypes 6, 11, 16, and 18, were collected. Definite clearance was defined as HPV DNA (same site) /antibodies for the same genotype undetected following a positive HPV DNA /antibodies test at baseline or month 3. Possible clearance was defined as HPV DNA (same site) /antibodies for the same genotype undetected at month 12 following a positive HPV DNA/antibodies test at month 6. Overall clearance was defined as either definite or possible clearance. The agreement between HPV DNA clearance and antibodies clearance was calculated. Results: A total of 183 MSM were included (median age: 19 years, interquartile [IQR]: 18 to 20). At the anus, overall clearance rate was 21.6 (95 % confidence interval[CI]: 7.9 to 47.0), 44.8 (19.3 to 88.3), 51.9 (20.9 to 106.9) and 33.7 (7.0 to 98.5) per 1000 person months (PM) for HPV 6, 11, 16 and 18. At the penis, overall clearance rate was 64.5 (13.3 to 188.5), 71.3 (14.7 to 208.2), 96.5 (31.3 to 225.3) and 333.3 (8.4 to 1857.2) per 1000 PM for HPV 6, 11, 16 and 18. For antibodies, overall clearance rate was 22.2 (9.6 to 43.7), 18.8 (3.9 to 55.0), 10.8 (0.3 to 60.1) and 19.0 (2.3 to 68.8) per 1000 PM. Agreement between anal/penile HPV DNA clearance and antibodies clearance was low: kappa = -0.18 (95 % CI: −0.28 to 0.08)/-0.13 (−0.24 to −0.02), 0.04 (−0.29 to 0.36)/0.22 (−0.32 to 0.76), −0.10 (−0.27 to 0.08)/-0.14 (−0.37 to 0.10) and −0.14 (−0.28 to 0.01)/-0.14 (−0.33 to 0.06) for HPV 6, 11, 16 and 18, respectively. Conclusion: Clearance rates of HPV DNA were low and varied by genotypes and anatomical sites among adolescent MSM. Antibodies against HPV were stable during the study period.

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer remain unclear. Methods: We retrospectively collected mammography records of an HR+/HER2− breast cancer cohort (n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of low-moderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions. Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor (ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2− breast cancer.

Abstract Background As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China’s National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. Methods A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. Results Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P

Abstract The progression of heart failure (HF) is complex and involves multiple regulatory pathways. Iron ions play a crucial supportive role as a cofactor for important proteins such as hemoglobin, myoglobin, oxidative respiratory chain, and DNA synthetase, in the myocardial energy metabolism process. In recent years, numerous studies have shown that HF is associated with iron dysmetabolism, and deficiencies in iron and overload of iron can both lead to the development of various myocarditis diseases, which ultimately progress to HF. Iron toxicity and iron metabolism may be key targets for the diagnosis, treatment, and prevention of HF. Some iron chelators (such as desferrioxamine), antioxidants (such as ascorbate), Fer-1, and molecules that regulate iron levels (such as lactoferrin) have been shown to be effective in treating HF and protecting the myocardium in multiple studies. Additionally, certain natural compounds can play a significant role by mediating the imbalance of iron-related signaling pathways and expression levels. Therefore, this review not only summarizes the basic processes of iron metabolism in the body and the mechanisms by which they play a role in HF, with the aim of providing new clues and considerations for the treatment of HF, but also summarizes recent studies on natural chemical components that involve ferroptosis and its role in HF pathology, as well as the mechanisms by which naturally occurring products regulate ferroptosis in HF, with the aim of providing reference information for the development of new ferroptosis inhibitors and lead compounds for the treatment of HF in the future.

Abstract Background Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. Methods Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. Results A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn’s disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn’s disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. Conclusions Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn’s disease, and ulcerative colitis).

Background: FAM110B belongs to the family that has a 110 sequence similarity (FAM110) and is located in the centrosome and mitotic spindle. FAM110B has been linked to tumor cell growth in earlier research. Uncertainty exists regarding FAM110B’s function within the tumor microenvironment is unclear as well as pan-cancer.Methods: In order to assess the variation in FAM110B expression within normal and pan-cancer tissues, we combined the TCGA and GTEx databases. The cBioPortal database and the GSCALite platform were used to examine the variation in genome and methylation alteration of FAM110B. Cox regression, Kaplan-Meier, and SangerBox were employed to examine the clinical features and prognosis of FAM110B and pan-cancer. The purpose of the correlational research was to investigate the associations within immunerelated genes, tumor mutation burden, microsatellite instability, immune-related genes, and immunological checkpoints and FAM110B expression. ESTIMATE, EPIC, QUANTISEQ, and MCPCOUNTER methods were used to calculate the interaction among FAM110B expression as well as the tumor immune microenvironment. The immunoinfiltration and function of FAM110B were analyzed by single-cell databases (TISCH and CancerSEA). Finally, we evaluated the sensitivity of FAM110B to small-molecule medications through GDSC and CTRP databases.Results: The transcription and protein expression of FAM110B varies significantly throughout cancer types, and this has predictive value for the prognosis of some tumors; including brain lower grade glioma (LGG), stomach adenocarcinoma (STAD), pancreatic adenocarcinoma (PAAD), etc. In the tumor microenvironment, the expression level of FAM110B was associated with immune cell infiltration, immune checkpoint immune regulatory genes, tumor mutational burden, and microsatellite fragility to a certain extent.Conclusion: This work investigates the possibility of utility of FAM110B as a marker to forecast pan-cancer immunotherapy response, providing a theoretical basis for cancer therapy.

Background: Zhiqiao Gancao decoction (ZQGCD) was created by Professor Gong Zhengfeng, a renowned Chinese medicine expert. Clinical studies have shown its efficacy in alleviating pain and enhancing lumbar function in intervertebral disc degeneration (IDD) patients. However, the precise mechanism of ZQGCD in treating IDD remains unclear. Methods: The active components of ZQGCD were identified using Liquid chromatography-tandem mass spectrometry (LC-MS/MS). A rat model of intervertebral disc degeneration was established, and rats in each group received ZQGCD for three weeks. Assessment parameters included hyperalgesia status, observation of intervertebral disc tissue degeneration and macrophage infiltration, and analysis of JAK2/STAT3 pathway protein expression in the intervertebral disc. Primary macrophage M1 polarization was induced using LPS, with cells treated using the JAK2 inhibitor (AZD1480) and ZQGCD to evaluate macrophage polarization, cellular supernatant inflammatory factors, and JAK2/STAT3 pathway expression. Macrophage supernatant served as a conditioned medium to observe its effects on the proliferation of nucleus pulposus cells (NPCs) and the expression of collagen II and MMP3 proteins. Results: A total of 81 active components were identified in ZQGCD. Following ZQGCD treatment, infiltrating macrophages in intervertebral disc tissues of model rats decreased, the content of M1 macrophages decreased, while the content of M2 macrophages increased, the expression of proinflammatory factors and pain-inducing factors in serum decreased, and the expression of substance P in intervertebral disc tissue decreased. Consequently, the intervertebral disc degeneration and hyperalgesia of rats were improved. In vitro studies revealed that LPS induced M1 macrophage polarization. By inhibiting the JAK2/STAT3 pathway, both JAK2 inhibitors and ZQGCD effectively suppressed M1 polarization, resulting in decreased levels of IL-1β, IL-6, TNF-α, and various other inflammatory factors. Consequently, this inhibition led to a delay in the degeneration of NPCs. Conclusion: There is macrophage infiltration in the intervertebral disc tissue of IDD rats, and JAK2/STAT3 pathway is activated, macrophages are polarized to M1 type, resulting in inflammatory microenvironment, leading to intervertebral disc degeneration and hyperalgesia. ZQGCD exhibited a delaying effect on IDD and improved hyperalgesia by inhibiting the JAK2/STAT3/macrophage M1 polarization pathway.

Background: Inflammation and immune factors are the core of intervertebral disc degeneration (IDD), but the immune environment and epigenetic regulation process of IDD remain unclear. This study aims to identify immune-related diagnostic candidate genes for IDD, and search for potential pathogenesis and therapeutic targets for IDD. Methods: Gene expression datasets were obtained from the Gene Expression Omnibus (GEO). Differential expression immune genes (Imm-DEGs) were identified through weighted gene correlation network analysis (WGCNA) and linear models for microarray data analysis (Limma). LASSO algorithm was used to identify feature genes related to IDD, which were compared with core node genes in PPI network to obtain hub genes. Based on the coefficients of hub genes, a risk model was constructed, and the diagnostic value of hub genes was further evaluated through receiver operating characteristic (ROC) analysis. Xcell, an immunocyte analysis tool, was used to estimate the infiltration of immune cells. Finally, nucleus pulposus cells were co-cultured with macrophages to create an M1 macrophage immune inflammatory environment, and the changes of hub genes were verified. Results: Combined with the results of WGCNA and Limma gene differential analysis, a total of 30 Imm-DEGs were identified. Imm-DEGs enriched in multiple pathways related to immunity and inflammation. LASSO algorithm identified 10 feature genes from Imm-DEGs that significantly affected IDD, and after comparison with core node genes in the PPI network of Imm-DEGs, 6 hub genes (NR1H3, SORT1, PTGDS, AGT, IRF1, TGFB2) were determined. Results of ROC curves and external dataset validation showed that the risk model constructed with the 6 hub genes had high diagnostic value for IDD. Immunocyte infiltration analysis showed the presence of various dysregulated immune cells in the degenerative nucleus pulposus tissue. In vitro experimental results showed that the gene expression of NR1H3, SORT1, PTGDS, IRF1, and TGFB2 in nucleus pulposus cells in the immune inflammatory environment was up-regulated, but the change of AGT was not significant. Conclusions: The hub genes NR1H3, SORT1, PTGDS, IRF1, and TGFB2 can be used as immunorelated biomarkers for IDD, and may be potential targets for immune regulation therapy for IDD.

Acne is a chronic inflammatory skin disease that primarily affects adolescents and is attributed to various factors, including hormonal changes, genetic predisposition, and environmental influences. It typically manifests in areas rich in sebaceous glands such as the face, chest, and back. Symptoms of acne can range from mild to severe and may present as pimples, pustules, nodules, cysts, and scarring. The appearance of acne can significantly impact both the physical and mental well-being of patients, potentially leading to feelings of anxiety, depression, and social withdrawal. The pathogenesis of acne is multifaceted involving genetic predisposition as well as environmental factors such as hormonal imbalances, inflammation, abnormal follicular sebaceous unit keratinization, proliferation of follicular microorganisms like Propionibacterium acnes, increased sebum production, and dietary influences. Traditional treatment methods for acne include topical drug therapy, oral drug therapy, photoelectric therapy, and chemical peeling. With ongoing research into the pathogenesis of acne, treatment methods are rapidly evolving with novel antibiotics, probiotics, biological agents, topical anti-androgen drugs, topical vitamin A acid metabolism blockers, antimicrobial peptides, immunotherapy, micro-needling, and micro-needling patches. This article aims to provide a comprehensive review of recent advancements in acne treatment.

Background: Oral squamous cell carcinoma (OSCC) stands as the predominant form of oral cancer, marked by a poor prognosis. Ferroptosis, a type of programmed cell death, plays a critical role in the initiation and progression of various cancers. Long non-coding RNAs (lncRNAs) are prominent in modulating cancer development. Nevertheless, the prognostic significance of ferroptosis-related lncRNAs (FRLs) in OSCC remains inadequately explored. This study aims to develop a predictive signature based on FRLs to forecast the prognosis of OSCC patients. Methods: We gathered expression profiles of FRLs along with clinical data from The Cancer Genome Atlas (TCGA) and FerrDb databases. A prognostic model based on 10 FRLs were constructed using Cox regression analyses with LASSO algorithms, and their predictive power was evaluated. Then, the model was used to investigate functional enrichment, immune landscape, m6A genes, somatic variations, and drug response in different risk cohorts of patients. Finally, the expression and function of STARD4-AS1 (steroidogenic acute regulator protein-related lipid transfer domain containing 4-antisense RNA 1), a potential prognostic marker for OSCC screening based on our bioinformatics analysis, were investigated in vitro. Results: We developed a signature comprising 10 FRLs to stratify patients into two risk cohorts according to their calculated risk scores. Patients classified as high-risk exhibited significantly poorer prognoses compared to those in the low-risk cohort. Furthermore, survival analysis, patient risk heat plot, and risk curve verified the accuracy of the signature. The role of this signature in OSCC was well investigated using immune microenvironment, mutational, and gene set enrichment analysis (GSEA). Moreover, seven drugs, including cisplatin and docetaxel, were identified as potential treatments for patients with high-risk cancers. In addition, the knockdown of STARD4-AS1 in OSCC cell lines markedly inhibited cell proliferation and migration and induced ferroptosis. Conclusion: Using this signature may improve overall survival predictions in OSCC, throwing new light on immunotherapies and targeted therapies. Moreover, STARD4-AS1 might regulate the process of ferroptosis and could be used as a novel biomarker of OSCC.

Objective Foraminoplasty is an important step in transforaminal endoscopic lumbar discectomy (TELD). A trephine is widely used in foraminoplasty. However, foraminoplasty using a trephine alone sometimes fails to remove the resected bone, resulting in the bone remaining in the foramen or spinal canal, which can potentially cause neurological irritation or injury. The objective of this study is to introduce a self‐designed tool, referred to as an anchoring drill, for use with a trephine in foraminoplasty in TELD and to evaluate its advantages. Methods A retrospective review was performed to identify patients who underwent L4–5 TELD between January 2019 to January 2022. Foraminoplasty was performed in all patients. Depending on whether the anchoring drill was used or not, patients were divided into two groups. Surgery‐related parameters and complications were reviewed. Visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) scores were also assessed for all patients. SPSS statistical software was used for statistical calculation. Results A total of 100 patients were included (55 in the anchoring drill group and 45 in the trephine group). The incidence of residual bone fragments after foraminoplasty of the anchoring drill group was 9.09%, which was lower than that of the trephine group, at 33.33% (p

Abstract Background Few studies have investigated healthy female individuals (HFI) and those with obstructed defecation syndrome associated with moderate rectocele in women (MRW), identified using three-dimensional high-resolution anorectal manometry (3D HRAM) parameters that correlate with age stratification. Objective We aimed to explore the clinical diagnostic values of the MRW and HFI groups using 3D HRAM parameters related to age stratification. Methods A prospective non-randomized controlled trial involving 128 cases from the MRW (treatment group, 68 cases) and HFI (control group, 60 cases) groups was conducted using 3D HRAM parameters at Tianjin Union Medical Center between January 2017 and June 2022, and patients were divided into two subgroups based on their ages: the ≥50 and < 50 years subgroups. Results Multivariate binary logistic regression analysis showed that age (P = 0.024) and rectoanal inhibitory reflex (P = 0.001) were independent factors affecting the disease in the MRW group. Compared to the HFI group, the receiver operating characteristic (ROC) curve demonstrated that the 3D HRAM parameters exhibited a higher diagnostic value for age (Youden index = 0.31), urge to defecate (Youden index = 0.24), and rectoanal pressure differential (Youden index = 0.21) in the MRW group. Conclusions Compared to the HFI group, the ROC curve of the 3D HRAM parameters suggests that age, urge to defecate, and rectoanal pressure differential in the MRW group have a significant diagnostic value. Because the Youden index is lower, 3D HRAM cannot be considered the gold standard method for diagnosing MRW.

Purposes Aiming at the problems of large computation and high reference quantity in existing traffic sign detection algorithms, in this paper we proposed a lightweight traffic sign detection algorithm based on improved YOLOv7. Methods The algorithm is divided into four parts: input, backbone network of feature extraction, neck network of feature fusion, and head network of target prediction. Large kernel convolution was introduced into the backbone network, which increases the effective receptive field and improves the ability of feature extraction. The detection of neck fusion coordinate attention, random pooling, and other methods can not only build channel attention and capture accurate position, but also improve the generalization ability of the network. In addition, a comprehensive depth-separable convolution module was proposed to extract image features by reducing the number of parameters and the radical sign. Results Experimental results show that the detection accuracy of the proposed algorithm on the CCTSDB2021 data set reaches 93.13%, and mAP also reaches 87.59%, which is a great improvement with respect to other methods of the same type. The network achieves a high accuracy rate under the condition of low parameter number and calculation amount, which can not only accurately capture the location information of traffic signs, but also achieve a high accuracy rate. At the same time, it can accurately predict the traffic signs.

This paper presents a novel multi-dimensional asymmetric game model for network attack–defense decision-making, called “Catch the Cyber Thief”. The model is built upon the concept of partially observable stochastic games (POSG) and is designed to systematically incorporate multi-dimensional asymmetry into network attack–defense problems. The attack agent is called a “thief” who wants to control a key host by exploring the unfamiliar network environment, and the defense agent is called a “police” who needs to catch the opponent before its goal is accomplished. The results indicate that the asymmetry of network attack and defense is not only influenced by attack and defense strategies but also by spatio-temporal factors such as the attacker’s initial position, network topology, and defense lag time. In addition, we have found that there may exist the “attack rhythm,” which makes “how to maintain a good attack rhythm” and “how to generate a robust defense strategy against different attackers” worth exploring. Compared with existing attack–defense game models, our game model can better generate a direct mapping relationship with real elements, enabling us to understand network attack and defense interactions better, recognize security risks, and design defense strategies that can directly serve real-world decision-making.

Abstract Aim To investigate the alterations of functional brain activity and connectivity in female nurses working on long‐term shifts and explore their correlations with work‐related psychological traits. Design An exploratory cross‐sectional study. Methods Thirty‐five female nurses working on long‐term shifts (shift nurses) and 35 female nurses working on fixed days (fixed nurses) were enrolled. After assessing the work‐related psychological traits, including burnout, perceived stress, anxiety, and depression of nurses, the fractional amplitude of low‐frequency fluctuations (fALFF) and region of interest (ROI)‐based functional connectivity (FC) analyses were performed to investigate the differences of brain spontaneous activity and functional connectivity between these two groups of nurses. Thereafter, correlations between the functional brain parameters (fALFF and FC) and clinical metrics were investigated among the shift nurses. Results Compared to fixed nurses, shift nurses had higher burnout, perceived stress and depression scores, lower fALFF in the right dorsolateral prefrontal cortex (dlPFC), left and right superior parietal lobule (SPL), bilateral anterior cingulate cortex (ACC), and higher fALFF in the right superior/middle temporal gyrus, as well as decreased FC between the right dlPFC (the selected ROI) and bilateral ACC, left and right inferior frontal/orbitofrontal gyrus (IFG/IOFG), right SPL, and left middle occipital gyrus (voxel‐level p

ObjectiveSexual health plays a vital role in healthy aging. However, little is known about the sexual attitudes of and the utilization of sexual and reproductive health services by older women in China. This article is based on a qualitative study of older Chinese women in suburban areas to examine their attitudes toward sexuality and their utilization of sexual and reproductive health services.MethodsFace-to-face semi-structured interviews were conducted with older women (ages 50 to 74) from suburbs of southern China. Participants were purposively sampled on a convenience basis and recruited when they were visiting community health facilities between June and December 2021. Inclusion criteria were older women aged 50 years and older who had sexual experience. A topic guide was used that focused on sexual activity, sexual attitudes, the utilization of sexual and reproductive health services, and the factors that influence these. Interviews were audio recorded and transcribed verbatim. We coded the data inductively and conducted a thematic analysis.ResultsTwenty-six Chinese women participated in the study. These older women had varying attitudes regarding sexual activity and its significance for older adults. The gender norms they held concerning sexual desire deemed that men had higher sexual desire than women. Most asymptomatic women did not actively seek sexual and reproductive health services. In most cases, women only sought professional services when they started to have sexual and reproductive health problems. Factors influencing the uptake of sexual and reproductive health services by older women were cost (affordability), availability, distance (accessibility), and conservative cultural norms towards sexuality.ConclusionThe attitudes of older women towards sexual activity are diverse. While some view sexual activity as common and essential for maintaining a sense of well-being in older age, others may hold different perspectives, considering it less significant. The utilization of sexual and reproductive health services by older Chinese women, except for when they were having a specific health issue, was low. Sexual health messages and services tailored for older women are needed.

Abstract Background At present, a large number of studies have found that long non-coding RNAs (lncRNAs) can be used as biomarkers for diagnosis and monitoring prognosis of hepatocellular carcinoma (HCC). The expression of lncRNA cancer susceptibility candidate 7 (CASC7) in HCC has rarely been studied. The purpose of this study was to explore the expression of CASC7 and its correlation with clinical features, and to further analyze its diagnostic value in HCC. Methods Serum samples were collected from 80 patients with HCC, 80 patients with chronic hepatitis B (CHB), and 80 healthy people. The expression level of serum CASC7 was detected by droplet digital PCR. Appropriate parametric and nonparametric tests were used for data analysis. Results The results showed that the expression of CASC7 in serum of patients with HCC was significantly higher than that of patients with CHB (median: 8.8 versus 2.2 copies/µl, p

Abstract Despite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.

Abstract Cyclophilins (CyPs) are involved in basic cellular functions and a wide variety of pathophysiological processes. Many CyPs have been identified as the aetiological agent and influence on the immune system. In the present study, the physicochemical and immunologic characteristics of three proteins of CyPs family (CyPA, CyPB and CyPE) were analyzed. The results indicated that CyPE showed a closer evolutionary relationship with allergenic CyPA. The structure and antigenicity of CyPE was significantly similar with CyPA. B-cell epitopes of CyPE and CyPA were predicted via multiple immunoinformatics tools. Three consensus B-cell epitopes of CyPE and CyPAs were finally determined. To verify results of in silico analysis, three proteins of CyPs family (CyPA, CyPE and CyPB) were cloned and expressed from Dermatophagoides pteronyssinus. ELISA results indicated that the positive reaction rates of the three proteins to patient serum are CyPA (21.4%), CyPE (7.1%), and CyPB (0%), illustrating that the IgE activity was exhibited in CypA and CypE excluding CyPB. Structure and immunoinformatics analysis demonstrated that the RNA-binding motif of CyPE could reduce the immunogenicity of PPIase domain of CyPE. The reason that CyPB has no IgE activity might be the structure mutation of CyPB on B-cell epitopes.

Abstract Background In 2003, China implemented free antiretroviral therapy (ART) for people living with HIV (PLHIV), establishing an eligibility threshold of CD4 50 (+ 7.8%, IRR = 1.078, 95% CI: 1.000–1.161; P = 0.046), heterosexual transmission (+ 12.4%, IRR = 1.124, 95% CI: 1.042–1.213; P = 0.002) and Southwestern China (+ 12.9%, IRR = 1.129, 95% CI: 1.055–1.208; P

Abstract Sonic hedgehog (Shh)-group medulloblastoma (MB) (Shh-MB) encompasses a clinically and molecularly distinct group of cancers originating from the developing nervous system with aberrant high Shh signaling as a causative driver. We recently reported that RNF220 is required for sustained high Shh signaling during Shh-MB progression; however, how high RNF220 expression is achieved in Shh-MB is still unclear. In this study, we found that the ubiquitin E3 ligases Smurf1 and Smurf2 interact with RNF220, and target it for polyubiquitination and degradation. In MB cells, knockdown or overexpression of Smurf1 or Smurf2 promotes or inhibits cell proliferation, colony formation and xenograft growth, respectively, by controlling RNF220 protein levels, and thus modulating Shh signaling. Furthermore, in clinical human MB samples, the protein levels of Smurf1 or Smurf2 were negatively correlated with those of RNF220 or GAB1, a Shh-MB marker. Overall, this study highlights the importance of the Smurf1- and Smurf2-RNF220 axes during the pathogenesis of Shh-MB and provides new therapeutic targets for Shh-MB treatment.

Abstract Considering both the DC fault ride‐through (FRT) and lightweight requirements of modular multilevel converter (MMC), this paper proposes a hybrid arm‐multiplexing modular multilevel converter (HAM‐MMC). The phase leg of the proposed MMC topology is divided into upper, middle, and lower arms, configured with full‐bridge submodules (FBSMs), half‐bridge submodules (HBSMs), and FBSMs, respectively. The time‐division multiplexing of middle arms between upper and lower arms is achieved by introducing arm selection switches, which considerably enhances the submodule utilization and thus minimizes the submodule number. The structure and zero voltage switching strategy of arm selection switches are presented, and a modified sorting algorithm is developed for capacitor voltage balance. The negative level output capability of FBSMs in upper and lower arms allows the DC voltage to be reduced in response to DC faults. Compared with the conventional hybrid MMC composed of HBSMs and FBSMs in a 1:1 ratio, the HAM‐MMC has the same power quality and DC FRT capability, but uses 25% fewer capacitors for lightweight. Simulation results demonstrate that the proposed HAM‐MMC can smoothly ride through DC voltage dip without interrupting power transmission, and can also rapidly resume normal operation after a zero‐voltage disturbance.

Objective: To investigate the effect of Niraparib, a clinically approved PARP inhibitor on the radiosensitivity of human lung and cervical cancer cells, and preliminarily explore the underlying mechanism. Methods: The human lung cancer cell line A549 and human cervical cancer cell line Siha were both treated with Niraparib for 1 ​h, or X-ray irradiation with 4 ​Gy, or Niraparib for 1 ​h combined with X-ray irradiation with 4 ​Gy. The effect was examined via measurements of cell proliferation by the cell counting kit-8 assay, and cell viability was detected by clone formation assays. Cell apoptosis and cell cycle distribution were investigated by flow cytometry. Results: In human lung and cervical cancer cell lines, Niraparib combined with radiation therapy significantly inhibited cell proliferation. The proportion of apoptotic cells in cell lines treated with Niraparib plus radiation (the combination group) was significantly higher compared with control, radiation, and Niraparib groups (P ​

To explore how traditional knowledge acts in the soil and water conservation in mountain agricultural systems, this study selects the Shexian Dryland Stone Terraced System (SDSTS) as the study area and employs the social-ecological system (SES) framework and ecosystem service (ES) evaluation methods in a joint way. Results of the action mechanism analysis show that local farmers, as the main actors, fully utilize a variety of traditional knowledge, which constitutes a set of action situations at both the field and landscape scales. This has not only improved the soil and water conservation capacity of the SDSTS, but also met the livelihood need of the local people. Evaluation of the action outcomes further displays that the stone terraced fields have a higher capacity for soil and water conservation than other land use types and they also show a superior performance in food production. This has led to the highest comprehensive benefit per unit area found in the stone terraced fields (1.69 × 104 dollars·ha−1), much higher than forests (3.48 × 103 dollars·ha−1) and the grasslands (2.58 × 103 dollars·ha−1) on slopes. The traditional knowledge is proven extremely important for the SDSTS to achieve sustainable development and effective measures are thus needed to promote its inheritance and development. The combination of these two methods makes up for the shortcomings of the current traditional knowledge research, which mainly focuses on qualitative description and is lack of systematic explanation of mechanisms. The con-joint use of them also provides theoretical reference and technical support for more case studies of traditional knowledge in the future.

Abstract Signal amplification is vitally important for sensing low‐dose X‐rays in medical diagnosis by amplifying the generated electric read‐out signal. However, the complexity of external amplification circuits hampers device miniaturization and portability, while integrating amplification functionality directly into sensors or detectors remains a significant and formidable challenge. In this work, a direct high‐gain X‐ray detector with facile electron drift speed manipulation is reported in perovskite single‐crystal film (SCF). By employing laser‐assisted nucleation, high‐quality MAPbBr3 SCF is fabricated with precise control of thickness from ≈20 to ≈500 µm and the area up to 3 by 2 cm, while the architecture of ITO/MAPbBr3/Au is constructed to form the Schottky junction in opposite polarity. With the assistance of applied bias, the space electric field over MAPbBr3 SCF can be tunable, which ensures the manipulation of charge carrier drift speed to form recirculation for internal gain. The resultant photodetector exhibits an ultrahigh sensitivity of 1.44 × 105 µC Gy−1 cm−2 with a gain of 5.14 × 105, an ultralow detection limit of 39.8 nGy s−1, and the X‐ray array imaging is achieved at a low dose rate of 5 µGy s−1. These results confirm the advance of high‐gain detectors in constructing sensing arrays for practical safe medical diagnosis.

Background Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2‐sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD. Methods and Results The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome‐wide association study of 8293 European participants. Summary‐level data on CAD were derived from a large genome‐wide association study (71 602 cases and 260 875 controls). We used the inverse‐variance‐weighted and Wald ratio methods as our main MR methods. The weighted median, simple median, maximum likelihood, MR pleiotropy residual sum and outlier, and MR‐Egger methods were performed as sensitivity analyses. Genetic colocalization analyses were conducted to validate the robustness of our MR findings. We found that genetically predicted circulating levels of macrophage migration inhibitory factor were associated with an increased risk of CAD at the Bonferroni‐adjusted level of significance (P

Background: Closed reduction is the preferred treatment for distal radius fractures. However, it requires a multiple experienced medical staff and manually maintaining stable traction is difficult. Additionally, doctors cannot assess the reduction status of a fracture in real-time through radiographic images, which may lead to improper reduction. Furthermore, post-fracture complications such as joint adhesion, stiffness, and impaired mobility pose a challenge for the doctors. So it is necessary to optimize the treatment process of the distal radius fracture through technological means.Methods: A robot-assisted closed reduction and rehabilitation system, which could assist doctors throughout the entire process of reduction, fixation, and rehabilitation of distal radius fractures, was developed. A mechanical system, composed of two grippers and a cooperative robotic arm, was used to grasp and tract the affected limb. A doctor controlled the robot through a joystick console and Windows application program. A biplane radiographic device was integrated into the system, which is not only convenient for doctors to view radiographic images of the fracture at any time but also for them to select the rotation axis of the wrist on the images before reduction and rehabilitation. Important information including the anteroposterior and lateral radiographic data and force and position parameters during the reduction and rehabilitation process were displayed on a graphic user interface.Results: Experimental results showed that the proposed robotic system can meet the technical requirements for the reduction and rehabilitation of distal radius fractures, all the rotation angles could be achieved, a maximum force of more than 50 N could be achieved in all traction directions, and the error in selecting the wrist joint rotation axis line using radiographic images was less than 5 mm.Conclusion: The developed robot-assisted system was shown to be suitable for closed reduction and rehabilitation of distal radius fractures, contributing a potential improvement in the quality of the procedures.

All-fiber coherent beam combiners based on the self-imaging effect can achieve a near-perfect single laser beam, which can provide a promising way to overcome the power limitation of a single-fiber laser. One of the key points is combining efficiency, which is determined by various mismatches during fabrication. A theoretical model has been built, and the mismatch error is analyzed numerically for the first time. The mismatch errors have been numerically studied with the beam quality and combining efficiency being chosen as the evaluation criteria. The tolerance of each mismatch error for causing 1% loss is calculated to guide the design of the beam combiners. The simulation results are consistent with the experimental results, which show that the mismatch error of the square-core fiber is the main cause of the efficiency loss. The results can provide useful guidance for the fabrication of all-fiber coherent beam combiners.

Objective: To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases.Methods: Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software.Results: A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren’s syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], p = 0.003), ACR50 (RR 1.80 [1.43, 2.26], p < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], p = 0.001), DAS28 (WMD −1.11 [−1.69, −0.52], p = 0.0002), reduce ESR (WMD −11.05 [−14.58, −7.51], p < 0.00001), CRP (SMD −1.52 [−2.02, −1.02], p < 0.00001), RF (SMD −1.65 [−2.48, −0.82], p < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], p < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD −1.62 [−2.20, −1.05], p < 0.00001), BASFI score (WMD −1.07 [−1.39, −0.75], p < 0.00001), VAS (WMD −2.01 [−2.83, −1.19], p < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD −1.71 [−2.44, −0.98], p < 0.00001; IGU only group: WMD −2.10 [−2.40, −1.81], p < 0.00001) and ESSDAI score (IGU + other therapy group: WMD −1.62 [−2.30, −0.94], p < 0.00001; IGU only group: WMD −1.51 [−1.65, −1.37], p < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer’s test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], p < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], p = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], p = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function.Conclusion: Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia.Systematic Review Registration: (CRD42021289489).

The aim of our study was to explore circular RNA (circRNA) expression profiles associated with human endometrial carcinoma (EC) and to analyse the molecular mechanisms involved in cancer development and their potential clinical importance. Differential expression profiles were revealed by Arraystar human circRNA microarray analysis. The results of the circRNA microarray were confirmed by quantitative real-time PCR. Interactions between circRNAs and microRNAs (miRNAs) were predicted using Arraystar’s miRNA target prediction software. The functions of the circRNA-miRNA coexpression network were identified by KEGG pathway analysis and GO analysis. Compared with para-tumorous tissues, 14 genes were significantly upregulated and 12 genes were significantly downregulated in EC tissues (P

ABSTRACTSince May 2022, human mpox cases have increased unexpectedly in non-endemic countries. The first imported case of human mpox in Hong Kong was reported in September 2022. Here we report the isolation and identification of MPXV from the vesicle swabs of this patient. In this research, the vesicle swabs were inoculated in Vero and Vero E6 cells. In addition to observing cytopathic effects (CPEs) in Vero or Vero E6 cells, the isolated virus was identified as mpox virus (MPXV) using quantitative Real-Time PCR (RT–PCR), transmission electron microscopy, and high-throughput sequencing. The experiment also assessed the cross-protective efficacy of sera from the smallpox vaccinated population and preliminarily assessed the inhibitory effect of anti-smallpox virus drugs against MPXV. CPEs can be observed on Vero E6 cells at 24 h and Vero cells at 48 h. The virus particles could be observed by transmission electron microscope, showing typical orthopoxvirus morphology. In addition, F3L and ATI genes which from MPXV A39R, B2R, HA genes which from orthopoxvirus were confirmed by conventional PCR and Sanger sequencing. The next generation sequencing (NGS) suggests that the MPXV strain belongs to B.1 branch of the West African linage, and has a high identity with the sequence of the 2022 ongoing outbreak. PRNT50 results showed that 26.7% of sera from individuals born before 1981 who had been immunized with smallpox were positive, but no MPXV-neutralizing antibodies were found in sera from individuals born later. All four anti-smallpox virus drugs evaluated demonstrated inhibition of mpox virus.

In order to study the bactericidal mechanism of slightly acidic electrolyzed water (SAEW) against Salmonella enteritidis, the effects of SAEW on cell membrane permeability, cell membrane integrity, reactive oxygen species (ROS), and intracellular ATP of Salmonella enteritidis were studied. The results showed that 2.04 lg (CFU/g) of Salmonella enteritidis on the surface of eggshells was inactivated after the SAEW treatment at the available chlorine concentration of 10 mg/L for 1 min. Moreover, relative to the control group, the conductivity of bacterial suspension of Salmonella enteritidis was increased from 13.78±0.13 ms/cm to 16.32±0.10 ms/cm (P

Abstract Background Current studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer. Methods ARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan–Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB). Results ARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score. Conclusions Our findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.

Background: The World Health Organization (WHO) declared monkeypox a “public health emergency of international concern” on 23 June 2022. However, there is a lack of data on monkeypox perceptions among medical workers. The purposes of this study were to evaluate perceptions, worries about monkeypox, attitudes towards monkeypox vaccination and their correlates among medical workers in China. Methods: Data were collected from medical practitioners using an online survey questionnaire between September 1 and September 30, 2022 in China. All the subjects completed an online questionnaire including general characteristics, perceptions/knowledge/worries about monkeypox, and attitudes towards monkeypox vaccination. Logistic regression was employed to examine the correlates of perceptions, worries about monkeypox, and attitudes toward monkeypox vaccination. Results: In total, this study sample included 639 medical workers. The mean age was 37.9 ± 9.4 years old. Approximately 71.8% of individuals reported perceptions of monkeypox, 56.7% worried about monkeypox, and 64.9% supported the promotion of monkeypox vaccination. Medical workers who were older than 50 years (aOR 3.73, 95%CI 1.01–13.85), worked in the Infectious Diseases/Dermatology/Venereal Diseases departments (3.09, 1.61–5.91), and provided correct answer to monkeypox transmission route (10.19, 5.42–19.17) were more likely to know about monkeypox/monkeypox virus before investigation. 30.7% reported that they were more worried about monkeypox than the coronavirus (COVID-19). Participants reported that the key population most in need of monkeypox vaccination were health practitioners (78.2%) and people with immunodeficiency (74.3%), followed by children (65.4%) and older adults (63.2%). Conclusion: Awareness of monkeypox was high and attitude towards the promotion of monkeypox vaccination was positive among medical staff in China. Further targeted dissemination of monkeypox common knowledge among health care providers might improve their precaution measures and improve the promotion of monkeypox vaccination among key populations.

With the progressive development of new energy technologies, high-power lithium batteries have been widely used in ship power systems due to their high-power density and low environmental pollution, and they have gradually become one of their main propulsion energy sources. However, the large-scale deployment of lithium batteries has also brought a series of safety problems to ship operations, especially the battery internal short circuit (ISC). Battery ISC faults are very hidden and unpredictable at the initial stage and often fail to be detected in time, ultimately leading to overheating, fire or even an explosion of the ship’s power system. Based on this, this paper proposes a fast and accurate method for early-stage ISC fault location and detection of lithium batteries. Initially, voltage variations across the lithium battery packs are quantified using curvilinear Manhattan distances to pinpoint faulty battery units. Subsequently, the localized characteristics of voltage variance among adjacent batteries are leveraged to detect an early-stage ISC fault. Simulation results indicate that the proposed method can quickly and accurately locate the position of 5 Ω, 10 Ω and 15 Ω ISC faulty batteries within the battery pack, as well as detect the abnormal batteries in a timely manner with considerable sensitivity and reliability.

Summary: The halide lead perovskite single crystals (HLPSCs) have great potential in gamma-ray detection with high attenuation coefficient, strong defects tolerance, and large mobility-lifetime product. However, mobile halide ions would migrate under high external bias, which would both weaken the gamma-ray response and cause additional noise. Here, we report the gamma-ray PIN photodiodes made of cascade HLPSCs including both ion-formed and electron-hole-formed electrical junctions that could suppress the ions migration and improve the charges collection. Our photodiodes based on cascade HLPSCs (MAPbBr3/MAPbBr2.5Cl0.5/MAPbCl3) show a wide halide-ion-formed depletion layer of ∼52 μm. The built-in potential along the wide ionic-formed junction ensures a high mobility-lifetime product of 1.1 × 10−2 cm2V−1. As a result, our gamma-ray PIN photodiodes exhibit compelling response to 241Am, 137Cs, and 60Co; the energy resolution can reach 9.4%@59.5keV and 5.9%@662keV, respectively. This work provides a new path toward constructing high-performance gamma-ray detectors based on HLPSCs.

Introduction Oropharyngeal squamous cell carcinoma (OPSCC) is increasingly prevalent and has significantly heterogeneous risks of survival for diagnosed individuals due to the inter-related risk factors. Precise prediction of the risk of survival for an individual patient with OPSCC presents a useful adjunct to therapeutic decision-making regarding the management of OPSCC. The aim of this systematic review, critical appraisal and meta-analysis is to assess prognostic prediction models for OPSCC and lay a foundation for future research programmes to develop and validate prognostic prediction models for OPSCC.Methods and analysis This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses Protocol statement. Based on predefined criteria, electronic databases including MEDLINE, Embase, Web of Science, the Cochrane Library and China National Knowledge Infrastructure (CNKI) will be searched for relevant studies without language restrictions from inception of databases to present. This study will systematically review published prognostic prediction models for survival outcomes in patients with OPSCC, describe their characteristics, compare performance and assess risk of bias and real-world clinical utility. Selection of eligible studies, data extraction and critical appraisal will be conducted independently by two reviewers. A third reviewer will resolve any disagreements. Included studies will be systematically summarised using appropriate tools designed for prognostic prediction modelling studies. Risk of bias and quality of studies will be assessed using the Prediction Model Risk of Bias Assessment Tool and the Transparent Reporting of a multivariable prediction model for individual prognosis or diagnosis. Performance measures of these models will be pooled and analysed with meta-analyses if feasible.Ethics and dissemination This review will be conducted completely based on published data, so approval from an ethics committee or written consent is not required. The results will be disseminated through a peer-reviewed publication.PROSPERO registration number CRD42023400272.

BackgroundFunctional constipation (FCon) is a common functional gastrointestinal disorder (FGID). Studies have indicated a higher likelihood of psychiatric disorders, such as anxiety, depression, sleep disturbances, and impaired concentration, among patients with FCon. However, the underlying pathophysiological mechanisms responsible for these symptoms in FCon patients remain to be fully elucidated. The human brain is a complex network architecture with several fundamental organizational properties. Neurological interactions between gut symptoms and psychiatric issues may be closely associated with these complex networks.MethodsIn the present study, a total of 35 patients with FCon and 40 healthy controls (HC) were recruited for a series of clinical examinations and resting-state functional magnetic imaging (RS-fMRI). We employed the surface-based analysis (SBA) approach, utilizing the Schaefer cortical parcellation template and Tikhonov regularization. Graph theoretical analysis (GTA) and functional connectivity (FC) analysis of RS-fMRI were conducted to investigate the aberrant network alterations between the two groups. Additionally, correlation analyses were performed between the network indices and clinical variables in patients with FCon.ResultsAt the global level, we found altered topological properties and networks in patients with FCon, mainly including the significantly increased clustering coefficient (CP), local efficiency (Eloc), and shortest path length (LP), whereas the decreased global efficiency (Eglob) compared to HC. At the regional level, patients with FCon exhibited increased nodal efficiency in the frontoparietal network (FPN). Furthermore, FC analysis demonstrated several functional alterations within and between the Yeo 7 networks, particularly including visual network (VN), limbic network (LN), default mode network (DMN), and somatosensory-motor network (SMN) in sub-network and large-scale network analysis. Correlation analysis revealed that there were no significant associations between the network metrics and clinical variables in the present study.ConclusionThese results highlight the altered topological architecture of functional brain networks associated with visual perception abilities, emotion regulation, sensorimotor processing, and attentional control, which may contribute to effectively targeted treatment modalities for patients with FCon.

Background: The World Health Organization declared monkeypox as a Public Health Emergency of International Concern. A cross-sectional online survey was conducted to understand beliefs, attitudes, perceived preventive measures, and vaccination acceptance related to monkeypox in the public in China. Methods: Between August 30 and September 15, 2022, we recruited adults through an online survey platform. Demographic characteristics, perceptions, common knowledge, concerns, attitudes, willingness to adopt preventive measures (including hygiene practices, social distancing, and travel avoidance), and vaccination acceptance related to monkeypox were collected. Logistic regression was used to assess correlates of concerns about monkeypox, willingness to adopt preventive measures, and vaccination acceptance. Results: 2135 participants were recruited (median age: 31.4 years). 62.7% were concerned about monkeypox. 33.2% were more concerned about monkeypox compared to COVID-19. Males (aOR 0.61, 95%CI 0.50–0.74), accessing monkeypox information from the Internet (0.77, 0.61–0.98), and willingness to adopt monkeypox vaccine (2.9, 2.38–3.53) were associated with concerns about monkeypox. Most participants were willing to adopt precautions (76.3% hygiene practices, 68.2% social distancing, 85.9% travel avoidance). Individuals who were concerned about monkeypox (hygiene practices: 2.09, 1.69–2.59; social distancing: 1.78, 1.46–2.16; travel avoidance: 1.74, 1.34–2.26) and had better knowledge about monkeypox (hygiene practices: 1.85, 1.48–2.31; social distancing: 2.17, 1.77–2.66; travel avoidance: 1.74, 1.34–2.26) were more likely to adopt precautions. 68.8% were willing to adopt monkeypox vaccine. Participants with older age (aged 40–49: 0.57, 0.38–0.85; aged 50 +: 0.50, 0.31–0.81), and higher income (¥6000–10,000: 0.61, 0.39–0.95; ≥¥10,000: 0.48, 0.30–0.77) were less likely to adopt the monkeypox vaccine. Being concerned more about monkeypox compared to COVID-19 (1.63, 1.31–2.02), and having better knowledge about monkeypox (1.34, 1.09–1.66) were associated with willingness to adopt vaccination. Conclusions: Compared with COVID-19, monkeypox attracted significantly less attention in the public in China, who currently have insufficient monkeypox knowledge. Interventions aimed at improving monkeypox knowledge and precautions among different groups of individuals in China are needed.

Abstract Gap junctions (GJs), which are composed of connexins (Cxs), provide channels for direct information exchange between cells. Cx expression has a strong spatial specificity; however, its influence on cell behavior and information exchange between cells cannot be ignored. A variety of factors in organisms can modulate Cxs and subsequently trigger a series of responses that have important effects on cellular behavior. The expression and function of Cxs and the number and function of GJs are in dynamic change. Cxs have been characterized as tumor suppressors in the past, but recent studies have highlighted the critical roles of Cxs and GJs in cancer pathogenesis. The complex mechanism underlying Cx and GJ involvement in cancer development is a major obstacle to the evolution of therapy targeting Cxs. In this paper, we review the post-translational modifications of Cxs, the interactions of Cxs with several chaperone proteins, and the effects of Cxs and GJs on cancer. Video Abstract

This paper considers a sales mode selection problem under revenue sharing contracts between resale and agency modes for risk-averse manufacturers with traditional retail channel, direct selling channel, and e-commerce platform channel. By considering the factors including price competition intensity, market share, revenue sharing ratio, commission rate, and degree of risk aversion, we construct leader-follower game models with manufacturers as leaders and traditional retailers and e-commerce platforms as followers. To obtain optimal solutions, we discuss conditions to ensure the upper and lower models to be convex and then give the optimal strategies for all members in the network. Through numerical experiments, we analyze the involved parameters’ impact on sales mode selection strategy and the changing trends of each member's optimal pricing and profit under different sales modes. The numerical results reveal the following revelations: The manufacturer should choose the agency mode when the commission rate is low and the direct selling channel has a large market share. If both the commission rate and degree of risk aversion are high, direct selling channels have a low market share, and price competition intensity is weak, the manufacturer should choose the resale mode. The degree of risk aversion has an effect on each member’s optimal decision. Regardless of which sales mode the manufacturer chooses, the optimal price of each member decreases as the degree of risk aversion increases. Under certain conditions, the manufacturer’s choice of agency mode can create win-win situations with supply chain members.

Abstract The immunity of patients who recover from coronavirus disease 2019 (COVID-19) could be long lasting but persist at a lower level. Thus, recovered patients still need to be vaccinated to prevent reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or its mutated variants. Here, we report that the inactivated COVID-19 vaccine can stimulate immunity in recovered patients to maintain high levels of anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NP) antibody titers within 9 months, and high neutralizing activity against the prototype, Delta, and Omicron strains was observed. Nevertheless, the antibody response decreased over time, and the Omicron variant exhibited more pronounced resistance to neutralization than the prototype and Delta strains. Moreover, the intensity of the SARS-CoV-2-specific CD4+ T cell response was also increased in recovered patients who received COVID-19 vaccines. Overall, the repeated antigen exposure provided by inactivated COVID-19 vaccination greatly boosted both the potency and breadth of the humoral and cellular immune responses against SARS-CoV-2, effectively protecting recovered individuals from reinfection by circulating SARS-CoV-2 and its variants.

In order to solve the problem of separation between consumer purchase and product experience in online sales, live streaming e-commerce came into being. However, the interaction of streamers is easy to cause consumers’ impulse consumption, which leads to the soaring return rate. In this context, how to make reasonable return policies to avoid the loss is an important issue for brands. This paper studies return policy selection for brands. We mainly focus on MCN (multi-channel network) click farming and customer disappointment aversion in the situations that the return-freight insurances are paid by brands or consumers or brands and MCN jointly. Three leader-follower models with brands as leaders and platforms and MCN as followers are established. To solve the above bilevel models, we discuss the conditions under which the upper and lower models are both convex and, based on these theoretical results, we give the optimal strategies for all members. Then, through numerical experiments, we analyze the impacts of customer disappointment aversion level, MCN’s ability, commission rate, brand’s return-freight insurance purchasing ratio, and other factors on each member’s optimal decision. The results show that the return policy in the situation of return-freight insurance paid by brand is suitable for a market with the high level of customer disappointment aversion; the return policy in the situation of return-freight insurance paid by consumers is applicable to the case of low customer disappointment aversion and high commission rate; the return policy in the situation of return-freight insurance paid by brand and MCN jointly is suitable for the case of low MCN capability and can effectively restrain the click farming from MCN.

Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment.Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis.Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%–81%], the proportion of surgery was 9% (95% CI 7%–12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%–47%), and the adverse events were 4% (95% CI 2%–6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) −2.46, 95% CI −3.30 to −1.63] and the herniated mass volume change (SMD −16.97, 95% CI −23.92 to −10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60–3.85). The results of sensitivity and publication bias analyses showed that the results were robust.Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).

Summary: Background: The ability to accurately identify the absolute risk of neurosyphilis diagnosis for patients with syphilis would allow preventative and therapeutic interventions to be delivered to patients at high-risk, sparing patients at low-risk from unnecessary care. We aimed to develop, validate, and evaluate the clinical utility of simplified clinical diagnostic models for neurosyphilis diagnosis in HIV-negative patients with syphilis. Methods: We searched PubMed, China National Knowledge Infrastructure and UpToDate for publications about neurosyphilis diagnostic guidelines in English or Chinese from database inception until March 15, 2023. We developed and validated machine learning models with a uniform set of predictors based on six authoritative diagnostic guidelines across four continents to predict neurosyphilis using routinely collected data from real-world clinical practice in China and the United States (through the Dermatology Hospital of Southern Medical University in Guangzhou [659 recruited between August 2012 and March 2022, treated as Development cohort], the Beijing Youan Hospital of Capital Medical University in Beijng [480 recruited between December 2013 and April 2021, treated as External cohort 1], the Zhongshan Hospital of Xiamen University in Xiamen [493 recruited between November 2005 and November 2021, treated as External cohort 2] from China, and University of Washington School of Medicine in Seattle [16 recruited between September 2002 and April 2014, treated as External cohort 3] from United States). We included all these patients with syphilis into our analysis, and no patients were further excluded. We trained eXtreme gradient boosting (XGBoost) models to predict the diagnostic outcome of neurosyphilis according to each diagnostic guideline in two scenarios, respectively. Model performance was measured through both internal and external validation in terms of discrimination and calibration, and clinical utility was evaluated using decision curve analysis. Findings: The final simplified clinical diagnostic models included neurological symptoms, cerebrospinal fluid (CSF) protein, CSF white blood cell, and CSF venereal disease research laboratory test/rapid plasma reagin. The models showed good calibration with rescaled Brier score of 0.99 (95% CI 0.98–1.00) and excellent discrimination (the minimum value of area under the receiver operating characteristic curve, 0.84; 95% CI 0.81–0.88) when externally validated. Decision curve analysis demonstrated that the models were useful across a range of neurosyphilis probability thresholds between 0.33 and 0.66 compared to the alternatives of managing all patients with syphilis as if they do or do not have neurosyphilis. Interpretation: The simplified clinical diagnostic models comprised of readily available data show good performance, are generalisable across clinical settings, and have clinical utility over a broad range of probability thresholds. The models with a uniform set of predictors can simplify the sophisticated clinical diagnosis of neurosyphilis, and guide decisions on delivery of neurosyphilis health-care, ultimately, support accurate diagnosis and necessary treatment. Funding: The Natural Science Foundation of China General Program, Health Appropriate Technology Promotion Project of Guangdong Medical Research Foundation, Department of Science and technology of Guangdong Province Xinjiang Rural Science and Technology（Special Commissioner）Project, Southern Medical University Clinical Research Nursery Garden Project, Beijing Municipal Administration of Hospitals Incubating Program.