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Abstract Neovaginas are surgically constructed to correct uterovaginal agenesis in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or as part of gender-affirming surgery for transfeminine individuals. Understanding the assembly of the neovaginal microbiota is crucial for guiding its management. To address this, we conducted a longitudinal study on MRKH patients following laparoscopic peritoneal vaginoplasty. Our findings reveal that the early microbial assemblage exhibited stochastic characteristics, accompanied with a notable bloom of Enterococcus faecalis and genital Mycoplasmas. While both the pre-surgery dimple microbiota and the fecal microbiota constituted the primary species pool, the neovaginal microbiota developed into a microbiota that resembled that of a normal vagina at 6–12 months post-surgery, albeit with a bacterial vaginosis (BV)-like structure. By 2–4 years post-surgery, the neovaginal microbiota had further evolved into a structure closely resembling with the homeostatic pre-surgery dimple microbiota. This concords with the development of the squamous epithelium in the neovagina and highlights the pivotal roles of progressive selective forces imposed by the evolving neovaginal environment and the colonization tropism of vaginal species. Notably, we observed that strains of Lactobacillus crispatus colonizing the neovagina primarily originated from the dimple. Since L. crispatus is generally associated with vaginal health, this finding suggests potential avenues for future research to promote its colonization.

Advanced metastatic cardia cancer is an intractable malignance with poor prognosis. It is often accompanied by upper digestive tract obstruction, which seriously affects the quality of patients. Therefore, effective relief of eating obstruction is an important goal in the treatment of cardia cancer. Immune checkpoint inhibitors (ICIs) have shown significant efficacy in cardia cancer, but only a small percentage of patients will benefit from them due to immune resistance. Oncolytic viruses have been shown to enhance the efficacy of ICIs by altering the immune microenvironment. This indicates that oncolytic virus has the potential value of overcoming the immune resistance of cardia cancer. Here, we present a case with local recurrent and multiple metastatic cardia cancer accompanied by eating obstruction. After 4 cycles of chemotherapy plus ICI therapy, the patient´s metastases were significant shrink, but the recurrent carida lesion were almost unchanged. Then we implemented exploratory local injection of recombinant human adenovirus type 5(H101) into recurrent cardia lesion by painless gastroscopy. Surprisingly, the cardia lesion shrank significantly, and the eating obstruction was greatly relieved. We also observed a significant increase of infiltrated CD4+T cells in biopsy tissues after H101 treatment. Our study not only conformed the value of oncolytic viruses to reverse ICI resistance in patients with gastric cancer, but also revealed its underlying impact on immune microenvironment.

Ferroptosis is considered an effective method to overcome drug-resistant tumors. This study aims to use three FDA-approved biological materials, human serum albumin, D-α-tocopherol succinate, and indocyanine green, to construct a novel biocompatible nanomaterial named HTI-NPs, exploring its effect in drug-resistant breast cancer (MCF-7/ADR cells). The research results indicate that HTI-NPs can selectively inhibit the proliferation of MCF-7/ADR cells in vitro, accompanied by upregulating transferrin receptor, generating reactive oxygen species, and downregulating glutathione peroxidase 4. Under laser irradiation, HTI-NPs can promote ferroptosis by inhibiting glutathione expression through photodynamic therapy. Notably, HTI-NPs exhibit good inhibitory effects on MCF-7/ADR xenograft tumors in vivo. In conclusion, HTI-NPs represent a biocompatible nanomaterial that induces ferroptosis, providing new insights and options for treating drug-resistant breast cancer.

The human genome harbors many endogenous retroviral elements, known as human endogenous retroviruses (HERVs), which have been integrated into the genome during evolution due to infections by exogenous retroviruses. Accounting for up to 8% of the human genome, HERVs are tightly regulated by the host and are implicated in various physiological and pathological processes. Aberrant expression of HERVs has been observed in numerous studies on exogenous viral infections. In this review, we focus on elucidating the potential roles of HERVs during various exogenous viral infections and further discuss their implications in antiviral immunity.

Previous studies demonstrated that EV71-infected cells secrete extracellular vesicles (EVs), facilitating the transfer of viral components to recipient cells and thereby promoting virus spread. Considering lipid signaling plays a crucial role in EVs-mediated cell-to-cell communication, we compared the lipid profile of EVs secreted from uninfected and EV71-infected cells (EVs-Mock and EVs-EV71) using the human rhabdomyosarcoma (RD) cell model. These two groups of EVs were purified by using size exclusion chromatography (SEC), respectively, and evaluated by transmission electron microscopy (TEM), nanoparticle tracking technology (NTA), and Western blotting (WB). In-depth lipidomic analysis of EVs identified 1705 lipid molecules belonging to 43 lipid classes. The data showed a significant increase in the lipid content of EVs after EV71 infection. Meanwhile, we deeply analyzed the changes in lipids and screened for lipid molecules with significant differences compared EVs-EV71 with EVs-Mock EVs. Altogether, we report the alterations in the lipid profile of EVs derived from RD-cells after EV71 infection, which may affect the function of the EVs in the recipient cells.

BackgroundNatural killer (NK) cells are proposed to participate in coronary artery disease (CAD) development. However, little is known about how CAD patients’ NK cells respond to different stimulatory factors in terms of proliferation capability.Methods and resultsTwenty-nine CAD patients’ peripheral blood NK cells were isolated and individually treated with IL-2, IL-12, IL-15, IL-18, IL-21, cortisone acetate, hydrocortisone, or ascorbic acid for 36 hours, followed by cell cycle analysis using flow cytometry. The ratio of S and G2/M phase cell number to total cell number was defined as a proliferation index (PrI) and used for proliferative capability indication. The results showed that these eight factors resulted in different life cycle changes in the 29 NK cell samples. Remarkably, 28 out of 29 NK cell samples showed an obvious increase in PrI upon ascorbic acid treatment. The serum lactate dehydrogenase (LDH) level of the 29 CAD patients was measured. The results showed a negative correlation between serum LDH level and the CAD patients’ NK cell PrI upon stimulation of interleukins, but not the non-interleukin stimulators. Consistently, a retrospective analysis of 46 CAD patients and 32 healthy donors showed that the circulating NK cell number negatively correlated with the serum LDH level in CAD patients. Unexpectedly, addition of LDH to NK cells significantly enhanced the production of IFN-γ, IL-10 and TNF-α, suggesting a strong regulatory role on NK cell’s function.ConclusionAscorbic acid could promote the proliferation of the CAD patients’ NK cells; LDH serum level may function as an indicator for NK cell proliferation capability and an immune-regulatory factor.

Abstract Objectives Silicosis people are at high risk of developing pulmonary tuberculosis. Whether silica exposure increases the likelihood of latent tuberculosis infection (LTBI) was not well understood, and potential factors involved in LTBI risk among silicosis people were not evaluated before. Thus, LTBI among silicosis people and potential risk factors for LTBI among silicosis people were evaluated in this study. Methods A cross-sectional study was undertaken for 130 miner workers with silicosis. The QFT-GIT was performed for LTBI detection. Results The LTBI was high to 31.6% (36/114) for silicosis participants, and 13.1% (13/99) had a history of tuberculosis. Drinking was associated with LTBI risk (OR = 6.92, 95%CI, 1.47–32.66, P = 0.015). Meanwhile, tunneling work was associated with an increased risk of LTBI compared with other mining occupations (OR = 3.91,95%CI,1.20–12.70, P = 0.024). Conclusions The LTBI rate of silicosis participants was high and more than 10% had a history of tuberculosis. Drinking alcohol and tunneling were independent risk factors for LTBI in silicosis participants.

ABSTRACTOXA-232 is one of the most common OXA-48-like carbapenemase derivatives and is widely disseminated in nosocomial settings across countries. The blaOXA-232 gene is located on a 6-kb non-conjugative ColKP3-type plasmid, while the dissemination of blaOXA-232 into different Enterobacterales species and the polyclonal dissemination of OXA-232-producing K. pneumoniae revealed the horizontal transfer of blaOXA-232. However, it’s still unclear how this non-conjugative ColKP3 plasmid could facilitate the mobilization of blaOXA-232. Here, we observed the in vivo intraspecies transfer of blaOXA-232 during a nosocomial outbreak of OXA-232-producing K. pneumoniae. We demonstrated the presence of ColKP3 OXA-232 plasmid in the outer membrane vesicles (OMVs) derived from clinical isolates, and OMVs could facilitate the horizontal transfer of blaOXA-232 among Enterobacterales. In contrast, for the most prevalent carbapenemase genes, including blaKPC-2 and blaNDM-1, though the presence of carbapenemase genes and plasmid backbones in the vesicular lumen was observed, OMVs couldn’t promote effective transformation, probably due to the low copy number of plasmids in clinical isolates and the low number of plasmids loaded into vesicles. Conjugation assay revealed that the epidemic IncX3 NDM-1 and IncFII(pHN7A8)/IncR KPC-2 plasmids were conjugative and could be horizontally transferred via independent conjugation or with the help of a co-existent conjugative plasmid. For the large-size and low-copy number conjugative plasmids carrying carbapenemase genes, OMVs-mediated gene exchange may only serve as an alternative pathway for horizontal transfer. In conclusion, diverse mobilization strategies were employed by plasmids harbouring carbapenemase genes, and plasmids display a proper choice of mobility pathway due to their individual properties.

ObjectiveWhite matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective.MethodsThe resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system.ResultsThe 149 CSVD patients included 20 cases of “Type I mismatch,” 51 cases of Type I match, 38 cases of “Type II mismatch,” and 40 cases of “Type II match.” Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between “Type I match” and “Type I mismatch”; the FT of States 1 and 4 differed significantly between “Type II match” and “Type II mismatch.” Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between “Type I match” and “Type I mismatch,” while the left MTA score differed between “Type II match” and “Type II mismatch.”ConclusionDifferent mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

AimTo investigate the efficacy and safety of combining Recombinant Human Endostatin Injection (marketed as Endo) with anti-PD-1 in elderly patients aged 80 and above with non-small cell lung cancer (NSCLC).MethodsRetrospective analysis of 181 patients with NSCLC aged 80 and above treated in the Department of Respiratory and Critical Care Medicine at Chaohu Hospital, affiliated with Anhui Medical University, from June 2019 to January 2024. Patients who received at least one cycle of combined Endo with anti-PD-1 were included based on inclusion criteria. Clinical and pathological data were collected, including complete blood count, liver and kidney function, electrocardiogram, coagulation function, thyroid function, cardiac enzymes, and whole-body imaging. Adverse events were recorded with a final follow-up on January 25, 2024. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety as a secondary endpoint.ResultsThis study involved 14 elderly patients with NSCLC aged over 80. Median progression-free survival (mPFS) was 102 days, and median overall survival (mOS) was 311 days. Subgroup analyses based on treatment cycles showed a non-significant 441-day mPFS increase in the long-term group (≥6 cycles, 5 patients) compared to the short-term group (

Abstract Background According to prenatal ultrasonographic studies, single umbilical artery may be present alone or in association with other fetal abnormalities. So far, the exact pathogenesis of bladder exstrophy is unclear. Some scholars believe that bladder exstrophy and cloacal exstrophy should be regarded as a disease spectrum to explore their pathogenesis. If bladder exstrophy and cloacal exstrophy are regarded as the same disease spectrum, then we can speculate that the single umbilical artery should have the probability of being accompanied by bladder exstrophy at the same time. Case presentation For the first time, we report a rare case of fetal bladder exstrophy with single umbilical artery in single pregnancy. This patient underwent targeted color Doppler ultrasound at 26 weeks of pregnancy which first suspected bladder exstrophy with single umbilical artery and fetal MRI for diagnosis at 38 + 3 weeks of pregnancy which confirmed the suspicion. After the diagnosis was confirmed, the patient was scheduled for a multidisciplinary discussion. Ultimately the patient opted for induced fetal demise at 38 + 5 weeks of pregnancy and the physical appearance of the fetal demise affirmed previous ultrasound and MRI examination results. Conclusions Our report is the first finding of single umbilical artery combined with bladder exstrophy in a singleton pregnancy. Accordingly, our case enhances the evidence that cloacal exstrophy and bladder exstrophy should be treated as the same disease spectrum. In addition, we conducted a literature review on the diagnostic progress of single umbilical artery combined with bladder exstrophy, hoping to provide useful references for the diagnosis of this disease.

Background: Colpocleisis is one of traditional surgical procedures for elderly and frail women with advanced pelvic organ prolapse. The occurrence of de novo urinary incontinence following colpocleisis was considered to impair the postoperative quality of life. The incidence of de novo urinary incontinence after colpocleisis has been reported to be ranging from 6.6 % to 27 %. There was an absence of prospective large-sample study to investigate the accurate incidence of de novo urinary incontinence following colpocleisis and the impact on the quality of life till now. Purpose: s The primary objective was to report the incidence of de novo urinary incontinence after colpocleisis. The second objectives were to evaluate the long-term quality of life in patients with de novo urinary incontinence, and to conduct detailed pre- and post-operative evaluations of lower urinary tract symptoms. Methods: This prospective study included 253 patients with symptomatic pelvic organ prolapse who underwent colpocleisis between 2009 and 2021. De novo urinary incontinence was defined as the occurrence of urinary incontinence 3 months postoperatively. All patients were required to complete the Urinary Distress Inventory questionnaire and the Urinary Impact Questionnaire for the evaluation of patients' quality of life, and the Patient Global Impression of Improvement questionnaire for the evaluation of patients’ satisfaction. Results: 245 patients (245/253, 96·8 %) completed the 3-month follow-up, and were included in the final analysis. The incidence of de novo urinary incontinence was 5.4 % (10/185). There was no significant difference in the Urinary Distress Inventory −6 scores (22.50 vs. 10.30, P = 0.276) or the subjective satisfaction rate (100 % vs. 98.9 %, P = 0.250) between the patients with or without de novo urinary incontinence at the long-term follow-up. The incidence of voiding difficulty was significantly reduced after colpocleisis (27.8 % vs. 0.0 %, P

BackgroundBoth the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group.ResultsThe NN group’s placental weight differed significantly from that of the other groups. The structure of NN group’s placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn’t be discounted.ConclusionIn diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn’t be ignored because of their tight relationships.

ObjectiveTo explore the mediating effect of depressive symptoms on occupational stress and work-related musculoskeletal disorders (WMSDs) in employees of petrochemical enterprises for developing intervention measures on WMSDs. MethodsTotally 4 066 employees were recruited with cluster sampling from a petrochemical enterprise in Jiangsu province for an online survey conducted during July – October 2021. Core Occupational Stress Scale (COSS), Patient Health Questionnaire-9 (PHQ-9)，and two questionnaire on demographics and WMSDs developed by Chinese researchers previously were used in the survey. Spearman rank correlation analysis was adopted to analyze the relationships between occupational stress, depression symptoms, and WMSDs; hierarchical regression analysis and bootstrap method were used to verify the mediating effect of depressive symptoms on the correlation between occupational stress and WMSDs. ResultsOf the 3 763 participants with valid responses, 2 934 (77.97%) were assessed as having WMSDs during past one year. The participants′ mean scores were 3.47 ± 3.17 on WMSDs and 10.04 ± 5.99 on depressive symptoms; the mean score on occupational stress was 45.79 ± 9.48, with the dimensional scores of 19.81 ± 3.75 on social support, 15.85 ± 4.94 on organization and reward, 12.35 ± 3.39 on demand and effort, and 4.62 ± 1.80 on autonomy, respectively. Spearman rank correlation analysis revealed following significant correlations among partici-pants′ scores on WMSDs, occupational stress and its dimensions, and depression symptoms: (1) positive correlations of WMSDs with overall occupational stress (r = 0.334), occupational stress dimensions of organization and reward (r = 0.284) and demand and effort (r = 0.202), and depression symptoms (r = 0.463) (P < 0.01 for all); (2) negative correlations of WMSDs with occupational stress dimensions of social support (r = – 0.256) and autonomy (r = – 0.141) (both P < 0.01); (3) positive correlations of depression symptoms with overall occupational stress (r = 0.621), occupational stress dimensions of organization and reward (r = 0.540) and demand and effort (r = 0.410) (P < 0.01 for all); (4) negative correlations of depression symptoms with social support (r = – 0.419) and autonomy (r = – 0.196) (both P < 0.01); (5) positive correlations of overall occupational stress with occupational stress dimensions of organization and reward (r = 0.848) and demand and effort (r = 0.639) (both P < 0.01); and (6) negative correlations of overall occupational stress with occupational stress dimensions of social support (r = – 0.648) and autonomy (r = – 0.310) (both P < 0.01). The results of mediating effect analysis showed that depressive symptoms had a partial mediating effect on the correlations of WMSDs with occupational stress dimensions of social support (effect value = – 0.137; confidence interval [CI]: –0.155, – 0.120; effect percentage = 72.87%) and demand and effort (effect value = 0.177; CI: 0.159, 0.196; effect percentage = 78.67%) but a complete mediating effect on the correlations of WMSDs with occupational stress dimensions of organization and reward (effect value = 0.146; CI: 0.131, 0.160; effect percentage = 90.12%) and autonomy (effect value = – 0.126; CI: – 0.158, – 0.094; effect percentage = 98.44%). ConclusionAmong the employees in a petrochemical enterprise in a province of China, the detection rate of WMSDs was high and depressive symptoms showed a mediating effect on the correlation of occupational stress with WMSDs, suggesting that the prevalence of WMSDs could be decreased through intervention on depression symptoms in the occupational population.

Abstract Background Universal social medical insurance coverage is viewed as a major factor in promoting social integration, but insufficient evidence exists on the integration of elderly rural migrants (ERM), generally aged 60 years and above, in low- and middle-income countries. To address this problem, we explore the relationship between the location of social medical insurance (SMI), such as a host city, and social integration in the context of Chinese ERM. Methods This study is based on data from the 2017 National Internal Migrant Dynamic Monitoring Survey in China. The study participants were Chinese ERM. An integration index was constructed to measure the degree of social integration in a multi-dimensional manner using a factor analysis method. This study used descriptive statistics and one-way analysis of variance to explore the differences in social integration between ERM with SMI from host cities and hometowns. Stepwise multiple linear regression analysis was used to test the correlation between SMI location and social integration level in the overall sample. Finally, the results were verified by propensity score matching. Results It was found that 606 (18.2%) of the insured ERM chose host city SMI, while 2727 (81.8%) chose hometown SMI. The level of social integration was lower among ERM with hometown SMI (-1.438 ± 32.795, F = 28.311, p ≤ 0.01) than those with host city SMI (6.649 ± 34.383). Among the dimensions of social integration, social participation contributed more than other factors, with a contribution rate of 45.42%. Host city SMI increased the probability of the social integration index by 647% among ERM (k-nearest neighbor caliper matched (n = 4, caliper = 0.02), with a full sample ATT value of 6.47 (T = 5.32, SE = 1.48, p

BackgroundCumulative fatigue without intervention will seriously threaten the physical and mental health of workers. Shift work and life satisfaction are strongly associated with fatigue accumulation. ObjectiveTo explore the effects of life satisfaction, shift work, and their interaction on cumulative fatigue in petrochemical employees, and to provide a scientific basis for preventing cumulative fatigue. MethodsAll staff of a petrochemical enterprise were selected by cluster sampling for a cross-sectional study from July to October 2021 in Jiangsu Province. A questionnaire designed by the project team was used to collect information on shift work; and life satisfaction and cumulative fatigue were investigated by the World Health Organization Five-item Well-Being Index and the Self-diagnosis Checklist for Assessment of Worker’s Fatigue Accumulation respectively. A logistic regression model was used to analyze the influences of life satisfaction and shift work on cumulative fatigue. Multiplicative and additive models were applied to analyze the interaction effect of life satisfaction and shift work. ResultsA total of 4066 questionnaires were returned, of which 3763 were valid, with an effective recovery rate of 92.5%. The percentage of cumulative fatigue in the petrochemical employees was 63.2% (2377/3763), and the percentages of low life satisfaction and shift work in the petrochemical employees were 53.6% (2016/3763) and 54.2% (2041/3763), respectively. The results of univariate analysis showed no significant difference in cumulative fatigue among different marital status groups (P=0.176), and there were statistically significant differences in cumulative fatigue among the petrochemical employees in different groups of age, gender, educational level, average monthly income, job title, length of service, working hours, night shift, smoking, drinking, physical exercise, life satisfaction, and shift work (P

ObjectiveTo explore the prevalence and early health effects of occupational stress among employees in a petrochemical enterprise for providing evidence to the implementation of relevant interventions in the employees. MethodsAn online self-administered questionnaire survey was carried out among 4 066 working employees of a petrochemical enterprise in Nanjing, Jiangsu province during September – October 2021. The Core Occupational Stress Scale (COSS)， Patient Health Questionnaire-9 (PHQ-9), Self-Rating Anxiety Scale (SAS)，the Five-Item World Health Organization Well-Being Index (WHO-5), Self-Administrated Sleep Questionnaire (SSQ)，and scales for fatigue accumulation and musculoskeletal disorders assessment were used in the survey. ResultsFor the 3 763 employees finally included in the analysis, 1 143 (30.4%) were assessed as having occupational stress. Among all the occupationally stressed employees, 607 (53.1%), 256 (22.4%), and 280 (24.5%) were judged as having mild, moderate, and severe occupational stress; the number (percentage) of the employees detected with abnormal conditions was 1 670 (44.4%) for depressive symptoms, 1 338 (35.6%) for anxiety symptoms, 2 016 (53.6%) for low life satisfaction, 1 548 (41.1%) for insomnia, 2 377 (63.2%) for fatigue accumulation, and 2 934 (78.0%) for musculoskeletal disorders, respectively. After adjusting for gender, age, education, marital status, average monthly income, job title, job type, working years of specific job type, weekly working hours, and work shift status，the results of unconditional multivariate logistic regression analysis showed that compared to those without occupational stress, the employees with occupational stress of different severity were at significantly increased risks of depressive symptoms (odds ratio [OR] = 3.582, 6.114 and 14.016 for the employees with mild, moderate or severe occupational stress), anxiety symptoms (OR = 4.268, 4.429 and 9.365), low life satisfaction (OR = 2.790, 2.896 and 7.849), insomnia symptoms (OR = 2.425, 3.033 and 5.218), fatigue accumulation (OR = 4.806,8.818 and 18.017), and musculoskeletal disorders (2.189, 2.381 and 4.367). ConclusionThe detection rate of occupational stress was relatively high and the stress exerted early adverse effects on health among employees of a petrochemical enterprise in Nanjing city .

Photocatalytic reduction of CO2 is considered as a kind of promising technologies for solving the greenhouse effect. Herein, a novel hybrid structure of g-C3N4/ZnO/Ti3C2 photocatalysts was designed and fabricated to investigate their abilities for CO2 reduction. As demonstration, heterojunction of g-C3N4/ZnO can improve photogenerated carriers’ separation, the addition of Ti3C2 fragments can further facilitate the photocatalytic performance from CO2 to CO. Hence, g-C3N4/ZnO/Ti3C2 has efficiently increased CO production by 8 and 12 times than pristine g-C3N4 and ZnO, respectively. Which is ascribed to the photogenerated charge migration promoted by metallic Ti3C2. This work provides a guideline for designing efficient hybrid catalysts on other applications in the renewable energy fields.

Abstract Introduction Neurofibromatosis (NF) is an inherited disease and a benign tumor originating from nerve sheath cells. Neurofibromatosis type I (NF1) is the most common type, and most cases are characterized by neurofibromas. Neurofibromas in NF1 are mainly treated by surgery. Our study explores the risk factors for intraoperative hemorrhage in Type I neurofibromatosis patients who underwent neurofibroma resection. Methods A cross-sectional comparison of the patients who had undergone resection of neurofibroma for NF1. Data regarding patient characteristics and data about operative outcomes were recorded. The definition of intraoperative hemorrhage group was the intraoperative blood loss greater than 200 ml. Results Of 94 eligible patients, 44 patients were in the hemorrhage group and 50 patients were in the non-hemorrhage group. Multiple logistic regression analysis demonstrated that the area of excision, classification, surgical site, primary surgical, and organ deformation were significant independent predictors of hemorrhage. Conclusion Early treatment can reduce the tumor cross-sectional area, avoid organ deformation, and reduce intraoperative blood loss. For plexiform neurofibroma or neurofibroma of the head and face, the amount of blood loss should be predicted correctly, and preoperative evaluation and blood preparation should be paid more attention to.

To address the issues of high cost, low welding efficiency, and complex processes in vacuum brazing, we proposed a method of electromagnetic ultrasonic (EU)-assisted brazing with Al-12Si solder to join SiC ceramic and TC4 alloy. The results showed that the maximum magnetic induction strength (MIS) on the surface of the liquid solder was 0.629 T when subjected to a static and alternating magnetic field (MF). Additionally, the combined action of MF and eddy current generated a downward Lorentz force (LF) in the liquid solder, with the maximum LF in the horizontal and vertical directions being 48.91 kN m−3 and 60.93 kN m−3, respectively. Under the influence of an EU wave, the liquid solder exhibited capillary filling (CF) behavior. At 26 ms, the maximum length of CF was 12.21 mm.

Domestic and international risk shocks have greatly increased the demand for systemic risk management in China. This paper estimates China’s multi-layer financial network based on multiple financial relationships among banks, assets, and firms, using China’s banking system data in 2021. An improved PageRank algorithm is proposed to identify systemically important banks and other economic sectors, and a stress test is conducted. This study finds that China’s multi-layer financial network is sparse, and the distribution of transactions across financial markets is uneven. Regulatory authorities should support economic recovery and adjust the money supply, while banks should differentiate competition and manage risks better. Based on the PageRank index, this paper assesses the systemic importance of large commercial banks from the perspective of network structure, emphasizing the role of banks’ transaction behavior and market participation. Different industries and asset classes are also assessed, suggesting that increased attention should be paid to industry risks and regulatory oversight of bank investments. Finally, stress tests confirm that the improved PageRank algorithm is applicable within the multi-layer financial network, reinforcing the need for prudential supervision of the banking system and revealing that the degree of transaction concentration will affect the systemic importance of financial institutions.

Macrophages and neutrophils are the main components of the innate immune system and play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis in the tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic tumor killing effects and orchestrate effective anti-tumor immune responses with proper stimulation and modification. Therefore, macrophages and neutrophils have strong potential in cancer immunotherapy. In this review, we briefly outlined the applications of macrophages or neutrophils in adoptive cell therapies, and focused on chimeric antigen receptor (CAR)-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns). We summarized the construction strategies, the preclinical and clinical studies of CAR-Ms and CAR-Ns. In the end, we briefly discussed the limitations and challenges of CAR-Ms and CAR-Ns, as well as future research directions to extend their applications in treating solid tumors.

BackgroundStudies have demonstrated that high iron status is positively associated with gestational diabetes mellitus (GDM), implying that iron overload and ferroptosis play important roles in the development of GDM. The aim of this study was to explore effective therapeutic drugs from traditional Chinese medicine (TCM)formulas for the treatment of GDM based on ferroptosis.MethodsIn this study, the presence of ferroptosis in the placenta was verified through clinical and experimental data, and key genes were subsequently screened for association with ferroptosis in the development of GDM. The analysis was based on transcriptome sequencing of datasets combined with differentially expressed genes (DEGs) analysis and weighted gene correlation network analysis (WGCNA); functional enrichment analysis was also performed. A protein−protein interaction (PPI) network was constructed and pivotal genes were identified using Cytoscape. Finally, traditional Chinese medicine (TCM)formulas related to treating GDM were collected, then the proteins corresponding to the key genes were molecularly docked with the small molecular structures of clinically proven effective herbal tonics, and molecular dynamic simulations were performed to select the best candidates for pharmacological compounds.ResultsElevated ferritin levels in patients with GDM were verified using clinical data. The presence of ferroptosis in placental tissues of patients with GDM was confirmed using electron microscopy and western blotting. Ninety-nine key genes with the highest correlation with ferroptosis were identified from DEGs and weighted gene co-expression network analysis (WGCNA). Analysis using the Kyoto Encyclopedia of Genes and Genomes demonstrated that the DEGs were primarily involved in the oxidative phosphorylation pathway. The key genes were further screened by PPI; two key genes, SF3B14 and BABAM1, were identified by combining the gene corresponding to protein structure and function, followed by molecular docking and molecular dynamic simulation. Coptis chinensis was proposed as the best candidate for herbal treatment at the molecular level.ConclusionThis data revealed the presence of ferroptosis in patients with GDM and identified possible modulatory roles of ferroptosis-related genes involved in the molecular mechanisms of GDM, providing new insights into the pathogenesis of GDM, which also provided new directions for the systematic optimization of TCM formulas for the management and targeted treatment of GDM.

Abstract Dust aerosols are produced by wind erosion, and it is widely accepted that dust aerosols can be produced only if the wind speed exceeds a certain threshold velocity, which is largely controlled by soil moisture content. The relative humidity (RH) in the air could affect soil moisture content, thereby impacting dust production indirectly. However, it is not clear if the RH can directly change dust aerosol production. Here we simulated dust production and show that the RH does play a direct role in affecting the production of dust aerosol in a quite complicated way, which can be explained by a hypothesis that the RH affects both the electrostatic forces and wet‐bonding forces between soil particles in opposite directions. The current formula for dust aerosol production flux does not include the direct RH effect, and this study strongly suggests that it could lead to significant errors in estimating dust production.

BackgroundCerebral small vessel disease (CSVD) is a cluster of microvascular disorders with unclear pathological mechanisms. The microbiota-gut-brain axis is an essential regulatory mechanism between gut microbes and their host. Therefore, the compositional and functional gut microbiota alterations lead to cerebrovascular disease pathogenesis. The current study aims to determine the alteration and clinical value of the gut microbiota in CSVD patients.MethodsSixty-four CSVD patients and 18 matched healthy controls (HCs) were included in our study. All the participants underwent neuropsychological tests, and the multi-modal magnetic resonance imaging depicted the changes in brain structure and function. Plasma samples were collected, and the fecal samples were analyzed with 16S rRNA gene sequencing.ResultsBased on the alpha diversity analysis, the CSVD group had significantly decreased Shannon and enhanced Simpson compared to the HC group. At the genus level, there was a significant increase in the relative abundances of Parasutterella, Anaeroglobus, Megasphaera, Akkermansia, Collinsella, and Veillonella in the CSVD group. Moreover, these genera with significant differences in CSVD patients revealed significant correlations with cognitive assessments, plasma levels of the blood-brain barrier-/inflammation-related indexes, and structural/functional magnetic resonance imaging changes. Functional prediction demonstrated that lipoic acid metabolism was significantly higher in CSVD patients than HCs. Additionally, a composite biomarker depending on six gut microbiota at the genus level displayed an area under the curve of 0.834 to distinguish CSVD patients from HCs using the least absolute shrinkage and selection operator (LASSO) algorithm.ConclusionThe evident changes in gut microbiota composition in CSVD patients were correlated with clinical features and pathological changes of CSVD. Combining these gut microbiota using the LASSO algorithm helped identify CSVD accurately.

BackgroundAtrial fibrill ation (AF) is a predominant public health concern in older adults. Therefore, this study aimed to explore the global, regional, and national burden of AF in older adults aged 60–89 between 1990 and 2019.MethodsThe morbidity, mortality, disability-adjusted life years (DALYs), and age-standardized rates of AF were refined from the Global Burden of Diseases study 2019. The epidemiological characteristics were assessed based on numerical values, age-standardized rates per 100,000 person-years, and estimated annual percentage changes (EAPC).ResultsGlobally, a total of 33.31 million AF cases, 219.4 thousand deaths, and 65.80 million DALYs were documented in 2019. There were no appreciable changes in EAPC from 1990 to 2019. The disease burden of AF differed significantly across different territories and countries. At the national level, China exhibited the highest number of incident cases [818,493 (562,871–1,128,695)], deaths [39,970 (33,722–46,387)], and DALYs [1,383,674 (1,047,540–1,802,516)]. At the global level, high body mass index (BMI) and high systolic blood pressure (SBP) were two predominant risk factors contributing to the proportion of AF-related deaths.ConclusionAF in older adults remains a major public health concern worldwide. The burden of AF varies widely at both national and regional levels. From 1990 to 2019, the cases of incidences, deaths, and DALYs have shown a global increase. The ASIR, ASMR, and ASDR have declined in the high-moderate and high SDI regions; however, the burden of AF increased promptly in the lower SDI regions. Special attention should be paid to the main risk factors for high-risk individuals with AF, which can help control systolic blood pressure and body mass index within normal limits. Over all, it is necessary to illustrate the features of the global AF burden and develop more effective and targeted prevention and treatment strategies.

Background: The Wnt/β-catenin signaling pathway plays crucial roles in tumor budding and the epithelial–mesenchymal transition (EMT). Myeloid ecotropic viral insertion site 3 (MEIS3)—a direct target of Wnt/β-catenin—promotes vagal neural crest cell migration into the gut tissue during development; however, its role in cancer progression remains unclear. In this study, the role of MEIS3 in colorectal cancer (CRC) progression was investigated. Methods: We analyzed the association between MEIS3 protein expression and the clinical stages of CRC patients, and the effect on tumor cell migration and invasion by wound healing and transwell assays. Finally, we analyzed the association between MEIS3 expression and the disease-free survival (DFS) and overall survival of CRC patients through Kaplan–Meier analysis. Results: We found that MEIS3 expression was strongly associated with CRC progression and could be employed to assess DFS in postoperative patients. MEIS3-positive cells were mainly distributed in the growth front and tumor–stroma interface of the CRC tissues, which contain abundant EMT-active and tumor budding cells dominating cancer metastasis. Moreover, MEIS3 promoted CRC cell migration and invasion by regulating effectors including laminin subunit beta 1, matrix metalloprotein 2, and vimentin. MEIS3 protein expression increased with CRC progression according to the clinical stage, which could be used as a biomarker to stratify CRC patients. The 5-year DFS of MEIS3-high patients was poorer than that of MEIS3-low patients (40.6% vs. 61.7%; p < 0.0001). Moreover, the 5-year DFS of stage II patients with MEIS3-high expression (53.4%) was comparable to that of stage III patients with MEIS3-low expression (49.5%), while the 5-year DFS of MEIS3-high patients in stage III (30.9%) was comparable to that of stage IV patients (29.6%). Conclusions: This study showed that MEIS3 can promote cancer cell metastasis and thus may be a promising biomarker for higher rates of recurrence in postoperative patients with stage II/III CRC.

Abstract Background Headache accompanying ischemic stroke is considered an independent predictor of neurological deterioration. This meta-analysis aims to estimate the prevalence of ischemic stroke-related headaches and identify its risk factors in China. Methods PubMed, Embase, Cochrane Library database, Web of Science, PsycINFO, and four Chinese databases for the related publications were searched. Two researchers independently selected the literature, extracted the relevant data, and assessed its methodological quality. The meta-analysis applied a random-effects model with R software to calculate the pooled prevalence of ischemic stroke-related headaches in Chinese patients, and to merge the odds ratio (OR) of risk factors. Subgroup analysis, sensitivity analysis, and meta-regression analysis were conducted. Publication bias was assessed by a funnel plot and Egger test. Results Ninety-eight studies were eligible for inclusion. The overall pooled prevalence of ischemic stroke-related headache was 18.9%. Subgroup analysis showed that the prevalence of ischemic stroke related-headaches was higher among studies using self-report to diagnosis headache (18.9%; 95%CI, 8.9% to 40.2%), and those focused on age ≥ 55 years (19.7%; 95%CI, 14.9% to 25.9%), rural settings (24.9%; 95%CI, 19.7% to 31.6%). There were no significant differences in the headache prevalence between studies in the south and north, and inland and coastal studies. The prevalence of pre onset headache (13.9%) and tension-type headache (15.5%) and was higher compared with other types. History of headache (OR = 3.24; 95%CI, 2.26 to 4.65.), female gender (OR = 2.06; 95%CI, 1.44 to 2.96.), midbrain lesions (OR = 3.56; 95%CI, 1.86 to 6.83.), and posterior circulation stroke (OR = 2.13; 95%CI, 1.14 to 4.32) were major risk factors. Conclusion The prevalence of ischemic stroke-associated headache is high in China. In addition, women, presence of midbrain lesions, posterior circulation stroke and a history of migraine were high-risk factors for ischemic stroke-related headaches. Designing effective interventions to prevent or alleviated headaches is necessary to promote patients’ neurological recovery and quality of life.

Even though uterine torsion is a rare obstetric complication in humans, it has been linked to severe complications like placental abruption, uterine rupture, foetal bradycardia, or even death. Here, we present a rare case of maternal shortening and prolonged foetal bradycardia. The patient suffered from congenital malformations of the female genital tract, which were classified as a complete bicorporeal uterus, a double “normal” cervix, and a longitudinal non-obstructing vaginal septum (U3b/C2/V1). The patient had an emergency caesarean section due to suspected placental abruption. Uterine torsion was found during the surgery, and the postoperative recovery was good. Obstetricians should be aware of the possibility of uterine torsion as a complication of pregnancy to avoid a delayed diagnosis of uterine torsion, especially in patients with genital malformations. During the surgery, there could be serious damage to blood vessels and tissues around the uterus due to an unclear surgical field, and difficulties in exposing the uterine body should be considered.

Abstract Background Short‐rib thoracic dysplasia (SRTD) and Joubert syndrome (JS) are rare genetic ciliopathies, and individuals with either syndrome can manifest cerebellar malformation and variable developmental delays. However, neither of these conditions is easily diagnosed during pregnancy due to a limited fetal phenotype. Here, we investigated a fetus that was initially observed to have short limbs and polydactyly and discovered a compound heterozygous pathogenesis through exome sequencing (ES). Methods Simultaneous trio‐ES and chromosome microarray analysis was provided for the fetus. The presence and effects of these variants on splicing were further validated at the DNA and RNA levels. Results Only short limbs and post‐axial polydactyly of the fetus were detected during the second trimester. Two variants (c.3940+1G>A and c.3303G>A), affecting splicing of KIAA0586, were identified from amniocytes through ES and validated by Sanger sequencing. More intensive fetal monitoring was applied, and the fetus was also found to have deformed cerebellar malformation and a constricted thoracic cage. Conclusions Herein, we report the genetic pathogenesis of SRTD and/or JS associated with KIAA0586 in a fetus. The novel splicing variants observed expand the spectrum of KIAA0586 in SRTD and/or JS. Based on the genetic data and the distinct corresponding phenotypes discovered by imaging examination, a comprehensive diagnosis was made during pregnancy and more valuable prognostic information was provided for the parents.

Tumor-associated macrophages (TAMs) are the most abundant infiltrating immune cells in the tumor microenvironment (TME) and play an important role in tumor progression. Clinically, the increase of TAMs infiltration is linked to poor prognosis of patients with various cancer types. Multiple studies have demonstrated that reducing or reprogramming TAMs can inhibit the occurrence or development of tumors. Therefore, TAMs have been identified as novel targets for the treatment of cancer therapy. In this review, the origin, polarization, roles, and targeting of TAMs in malignancies, are discussed.

ObjectiveThis systematic review and meta-analysis compares the outcome between MMBC and unifocal breast cancer (UFBC), in order to provide a theoretical basis for the design of an appropriate clinical therapeutic strategy of MMBC patients.MethodsPubMed, Embase, The Cochrane Library, Web of science, CNKI, WanFang Data, CBM and VIP database were searched from inception to July 2021, and observational studies reporting the outcome of patients with MMBC and UFBC were included. We extracted or calculated the mortality rates of MMBC and UFBC patients; and obtained the hazard ratios; odds ratios; relative risks; and the corresponding 95% confidence intervals from the eligible studies. All the meta-analyses were conducted by using the Stata 15.0 software.Results31 eligible studies comprising a total of 15,703 individuals were included. The meta-analysis revealed that MMBC did not have a significant association with poor overall survival (HR=1.04, 95% CI=0.96-1.12), disease-free survival (HR= 1.07, 95% CI= 0.84-1.36), breast cancer-specific survival (HR=1.42, 95% CI= 0.89-2.27), recurrence-free survival (HR= 0.878, 95% CI= 0.652-1.182), local recurrence-free survival (HR= 0.90, 95% CI= 0.57-1.42), and contralateral breast cancer risk (RR= 0.908, 95% CI= 0.667-1.234). However, MMBC appeared to have a correlation with a slightly higher risk of death (OR=1.31, 95% CI=1.18-1.45).ConclusionPatients with MMBC appeared to have a higher risk of death, however, it may not be independently associated with poorer outcomes. Considering the inter-study heterogeneity and other limitations, our results need to be validated by further multicenter prospective studies with a large sample size in the future.

The World Health Organization (WHO) estimates that about one-third of people worldwide currently have a need for rehabilitation. This demand is expected to increase in the coming years due to changes in population health and characteristics. For example, with the intensification of global aging, the rehabilitation needs of patients with chronic diseases and disabilities, postoperative dysfunction, and cognitive impairment continue to grow, and emergencies such as conflicts, disasters, and epidemics may lead to a surge in rehabilitation needs. Early and sustained rehabilitation could reduce complications, improve function, and reduce disability in affected populations, but rehabilitation services are often underestimated due to underfunding and poor short-term outcomes. WHO sees rehabilitation as an essential part of achieving universal health coverage and the Sustainable Development Goals. With the development of China's economy and society and the trend of an aging population, the demand for rehabilitation therapists is growing rapidly. Since the development of rehabilitation education in China at the beginning of this century, great progress has been made in both the training mode and the number of people trained, especially in the construction of higher education of rehabilitation in related colleges and universities. Through descriptive qualitative analysis, this study collected information from national policy documents and official websites of colleges and universities on policies concerning degree systems, cultivating goals and ideas, courses, education internationalization, continuing education in practice, standardized training after graduation, the number of colleges and universities with rehabilitation therapy related majors in China, and summarizes the current situation of the development of rehabilitation personnel education in Chinese colleges and universities. Judging from the results, during the development of rehabilitation education, China has continuously improved in terms of policy support, educational goals and concepts, the number and quality of institutions, degree systems, and internationalization, while gradually adapting to China's development status. This also provides direction and feasible suggestions for China to improve the rehabilitation education development system and formulate a national rehabilitation education plan in the future to deal with the challenge of aging.

BackgroundFamily physicians play a key role in responding to the growing demand for primary healthcare due to aging. The work attitude of family physician team members (FPTMs) impacts their work efficiency and quality. Knowing how satisfied they are with their jobs can help identify potential directions and entry points for incentives. The purpose of this study is to analyze the job satisfaction status and influencing factors of grassroots health service personnel after the implementation of the family physician contract system in China.MethodsThe study conducted a cross-sectional survey with 570 FPTMs in three prefecture-level cities in the Shandong Province. Satisfaction was measured using 30 items across seven dimensions. Responses were recorded on a 5-point Likert scale. Descriptive statistical analysis was used to analyze the general information and satisfaction of FPTMs. Multiple linear regression analysis was used to analyze the factors influencing job satisfaction.ResultsThe overall job satisfaction among FPTMs was not high. Among the seven dimensions, interpersonal relationships had the highest satisfaction (4.10 ± 0.78), while workload had the lowest satisfaction (3.08 ± 0.56). The satisfaction levels of the three sample regions were different, and the results were opposite to their regional economic development levels. The results of the multifactor analysis showed that gender, income level, educational background, working years, daily working hours, number of training sessions per year and the proportion of performance pay had significant impact on overall job satisfaction.ConclusionsThe development of a family physician contract system has increased the workload of FPTMs. In addition to the implementation of the new policy, attention should be paid to the workload and working attitude of family physicians. The fundamental measures should focus on attracting more personnel to work at the grassroots level by accelerating education and training to solve the problem of insufficient health personnel at the grassroots level. Simultaneously, attention should be paid to the improvement of the medical staff's salary level and the need for self-promotion, such as training.

BackgroundDue to an increasing aging population, China has experienced a rapid expansion in its internal older migrant population who face greater health risks and who have a relatively high demand for health education. Public health education is an important means of preventing diseases and promoting health. However, many studies have focused on the utilization, with few studies examining the impact of public health education on the health of the older migrant population in China.ObjectivesThis study analyzed the impact of public health education on the health of the older migrant population in China.MethodsBased on data obtained from the National Migrant Population Health and Family Planning Dynamic Monitor Survey (2018), logistic models and propensity score matching were used to analyze the impact of public health education on the health of the older migrant population.ResultsThe self-assessed health of China's older migrant population was good, and the acceptance rate of public health education was 40.81%. The public health status of the older migrant population receiving public health education significantly improved (p < 0.05). After correcting for endogeneity among the variables, public health education increased the probability of improving the older migrant population's self-assessed health by 5.4–6.1% (p < 0.01). Heterogeneity analysis found that public health education had a greater impact on the health of older men with an education level of middle school and below, and especially on the older migrant population in the eastern region of China.ConclusionsPublic health education positively affected the health status of the older migrant population. The characteristics and preferences of the older migrant population involving different genders, regions, and educational levels need to be considered, public health education needs to be standardized, and appropriate education methods need to be adopted that suit the older migrant population. Reference suggestions are provided for improving the health level of the older migrant population.

BackgroundReliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD.Materials and methodsA prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain age-related imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers.ResultsThe gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R2 = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients.ConclusionBrain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients.

As the global economy continues to integrate, COVID-19 is affecting businesses around the world, causing the financial system to become more complicated. The complicated relationship between various agents in the financial system makes potential hazards more easily transmitted. Most studies of systemic risks have focused on single-layer networks, and macroeconomic fluctuations have not been quantified in multi-layer models of financial networks. In this paper, three different macroeconomic shock scenarios (showing upward, downward, and random trends) are constructed to affect the firm’s business activities, and a multi-layer financial network model is developed to simulate systemic risk under macroeconomic fluctuations. Firms with medium and high leverage and small asset sizes, as well as banks with smaller asset sizes and fewer bank-firm credit linkages, are found to be more likely to default. The study also found that average firm leverage exhibits two inflection points, causing banks’ default probabilities to “rise, then fall, and then rise,” with the inflection point value being the lowest under the upward trend of macroeconomics. In addition, the higher the ratio of firm loans to total bank assets, the more likely the bank is to default. Appropriate loan maturity extension has also helped to reduce systemic risk, especially in light of the macroeconomic downward trend. Furthermore, improving the capital adequacy ratio can reduce the bank’s default probability under macroeconomic fluctuations.

BackgroundThe need for rehabilitation therapy has increased dramatically with the aging of the population, the prevalence of non-communicable diseases, and the increase in the number of disabilities. Rehabilitation therapists are crucial to provide high quality rehabilitation therapy; however, there is a significant shortage of these professionals in China. One of the effective strategies to address this challenge is using the norm of the workforce for rehabilitation therapy, which is an index for assessing the personnel required in a facility. This research aimed to create a rehabilitation therapist-required norm under institutional perspective in Shandong Province, China, based on the Workload Indicators of Staffing Needs (WISN) method, which was created by the World Health Organization (WHO) in 1998 to analyse staff utilization at various levels of the health care system.MethodsWe conducted descriptive and quantitative research from October to November 2020 in the rehabilitation department of a tertiary hospital in Weifang City, China. Focus groups, online interviews, and document reviews were conducted to gather data and calculations of the WISN method performed.ResultsAdmission assessment, pre-treatment evaluation, rehabilitation therapy, post-treatment evaluation, and health education for patients were identified as the main priority group activities. Interviews and analysis of documents summarized five factors related to rehabilitation therapists' health service activities. In this study, the annual working time of each therapist was 1,776 h per year. The WISN method calculations showed that the norm of rehabilitation therapists in this tertiary hospital was 23 therapists. As the department had 13 therapists, there was a shortage of 10 therapists based on the WISN calculation, with a ratio of 0.57, which represented the actual compared to the ideal number of therapists.ConclusionWorkload pressure was high for therapists in this tertiary hospital. This model revealed a demand for ten more therapists in the rehabilitation department. The WISN method can help hospital administrators in therapist workforce monitoring, including in regard to therapists. Therefore, the WISN method should be embraced as part of hospital human resource planning and recruitment strategies to meet increasing rehabilitation needs.

Online discourse is widely used in diverse contexts of learning and professional training, but superficial interactions and digression often occur. In the face of these problems and the large-scale unstructured text data, the traditional way of learning analytics has been challenged in terms of providing timely intervention and feedback. In this paper, a workflow for automatically detecting in-service teachers’ cognitive engagement in an online professional learning community is described. Discourse data of 1834 in-service teachers involved in a teacher professional development program was collected and processed using the Word2vec toolkit to generate lexical vectors. The method of vector space projection was used to calculate the new information contained in each post, cosine similarity was used to calculate topic relevance, and cluster analysis was used to explore in-service teachers’ discourse characteristics. Results showed that in-service teachers’ average contribution was 4.59 posts and the average length of each post was 39.47 characters in Chinese. In the mathematics online professional learning community, the average amount of new information contained in each post was 0.221 and in-service teachers’ posts contained much new information in the early stages of online discourse. Most in-service teachers’ posts were relevant to the discussion topic. Cluster analysis showed three different groups of posts with unique characteristics: high topic relevance with much new information, high topic relevance with little new information, and low topic relevance with little new information. Finally, limitations are discussed and future research directions are proposed.

Abstract Background The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT. Patients and methods We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses. Results Of the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07–13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP. Conclusions Grade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.

In our continuing efforts toward the design of novel pentacyclic triterpene derivatives as potential anti-influenza virus entry inhibitors, a series of homogeneous heptavalent glycyrrhetinic acid derivatives based on β-cyclodextrin scaffold were designed and synthesized by click chemistry. The structure was unambiguously characterized by NMR, IR, and MALDI-TOF-MS measurements. Seven conjugates showed sufficient inhibitory activity against influenza virus infection based on the cytopathic effect reduction assay with IC50 values in the micromolar range. The interactions of conjugate 37, the most potent compound (IC50 = 2.86 μM, CC50 > 100 μM), with the influenza virus were investigated using the hemagglutination inhibition assay. Moreover, the surface plasmon resonance assay further confirmed that compound 37 bound to the influenza HA protein specifically with a dissociation constant of 5.15 × 10−7 M. Our results suggest the promising role of β-cyclodextrin as a scaffold for preparing a variety of multivalent compounds as influenza entry inhibitors.

In the fields of public health policy and public health care, advanced educational programs are an important strategy in dealing with public health crises. The COVID-19 pandemic has exposed the global need for skilled public health leaders and managers to address complex public health challenges, which requires the strengthening of public health education at the highest levels. This paper is a qualitative case study of a special educational program for doctors of public health in China. The program's educational objectives are in line with epidemic prevention and control. With the goal of developing the world's leading national public health management system, the Chinese government established an advanced academic program for public health crisis management. The program offers doctoral students a multidisciplinary degree based upon the theoretical knowledge of crisis management, supported by advanced training in the foundational concepts, theories, and practices of public health, and the study of basic medicine which provides the theoretical support for developing essential clinical skills. Program graduates develop the theoretical, practical, and leadership-related capabilities required for the management of national emergencies. The program introduced in this paper meets current epidemic prevention and control needs and should be considered by public health policy makers, leaders, and scholars in the discussion of advanced public health policy and health care education in China, including the development of an internationally recognized Doctor of Public Health program.

One of the key points of modeling noncircular particles in the discrete element method is the contact detection of particles. In this study, a general contact detection algorithm of two-dimensional particles with analytic shape functions is provided. The contact detection of particles with strictly convex shape function, such as ellipses and superellipses, is solved by Newton–Raphson method, and a grid method is provided to deal with heart-shaped particles. The grid method can be generalized into a particle system, in which the shape function is not convex. The accuracy and stability of the algorithm are verified by a series of tests. For the collision of a pair of ellipses with an aspect ratio of α = a/b = 1000, the efficiency is not worse than the Newton–Raphson method. For random packing under gravity, no residual kinetic energy is observed, and the force that acts on the bottom is equal to the gravity, that is, the system reaches a mechanical equilibrium state. After equilibrium, the process of hopper discharge is also simulated. The present method is suitable for arbitrarily shaped particles with analytic shape functions in two-dimensional cases. In addition to superellipses, the method can also be applied to other particle systems as long as the shape functions are given.

As immunotherapy has gained increasing interest as a new foundation for cancer therapy, some atypical response patterns, such as pseudoprogression and hyperprogression, have garnered the attention of physicians. Pseudoprogression is a phenomenon in which an initial increase in tumor size is observed or new lesions appear, followed by a decrease in tumor burden; this phenomenon can benefit patients receiving immunotherapy but often leads to premature discontinuation of treatment owing to the false judgment of progression. Accurately recognizing pseudoprogression is also a challenge for physicians. Because of the extensive attention on pseudoprogression, significant progress has been made. Some new criteria for immunotherapy, such as irRC, iRECIST and imRECIST, were proposed to accurately evaluate the response to immunotherapy. Many new detection indexes, such as ctDNA and IL-8, have also been used to identify pseudoprogression. In this review, the definition, evaluation criteria, mechanism, monitoring, management and prognosis of pseudoprogression are summarized, and diagnostic and treatment processes for patients with progression but with a suspicion of pseudoprogression are proposed; these processes could be helpful for physicians in clinical practice and enhances the understanding of pseudoprogression.

The discovery of Mn4+-doped red phosphors with a high quantum efficiency (QE) and good thermal stability is of great interest for plant cultivation lighting. Here, for the first time, a new highly efficient and thermally stable far-red-emitting phosphor Ca3-6y(NaLu)3yLiSbO6:Mn4+ (CNULS:Mn4+) is reported. When a far-red-emitting phosphor Ca3LiSbO6:Mn4+ (CLS:Mn4+) was prepared via the solid-state reaction method, its maximum internal and external QEs are only 39.5% and 23.1%, respectively. Through the chemical unit co-substitution of [Na+−Lu3+] for [Ca2+−Ca2+] in CLS:Mn4+, its luminescence properties can be improved tremendously and the internal and external QEs for the substitution amount of y = 3% are as high as 80.1% and 47.4%, respectively. The large luminescence enhancement is attributed to the increase of structural rigidity induced by lattice contraction. The CNULS:Mn4+ phosphor exhibits excellent thermal stability with the emission intensity at 423 K remaining 87% of the value at 298 K. The LED device fabricated with the CNULS:Mn4+ (y = 3%) phosphor can produce bright and stable far-red emission, which matches well with the absorption spectrum of phytochrome PFR. These results suggest that the CNULS:Mn4+ phosphor could be a promising far-red-emitting converter for plant growth as well as solid-state lighting.

The overuse of antibiotics has led to severe bacterial drug resistance. Blocking pathogen virulence devices is a highly effective approach to combating bacterial resistance worldwide. Type three secretion systems (T3SSs) are significant virulence factors in Gram-negative pathogens. Inhibition of these systems can effectively weaken infection whilst having no significant effect on bacterial growth. Therefore, T3SS inhibitors may be a powerful weapon against resistance in Gram-negative bacteria, and there has been increasing interest in the research and development of T3SS inhibitors. This review outlines several reported small-molecule inhibitors of the T3SS, covering those of synthetic and natural origin, including their sources, structures, and mechanisms of action.

Infection caused by Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is very common in communities and hospitals, which poses a great challenge to human health. Therefore, increasing attention has been paid to finding effective antimicrobial agents. Mansonone F is a natural compound which has an oxaphenalene skeleton and anti-S. aureus activity, but its sources are limited and its synthesis is difficult. Thus, IG1, a C9-substituent mansonone F analog, was assessed for its activity against Staphylococcus aureus and its mechanism of action was investigated. Antimicrobial susceptibility assays showed that IG1 has strong antibacterial activity against S. aureus, including MRSA, with minimum inhibitory concentrations (MICs) ranging from 0.5 to 2 μg/mL, which were very close to those of vancomycin, and these changed little, even with an increase in the amount of the inoculum. To further explore the antibacterial properties of IG1, time–kill experiments were conducted. Compared with vancomycin and moxifloxacin, treatment with different concentrations of IG1 reduced the viability of organisms in a very similar manner and the reduction was not significant, which indicated that IG1 is a potentially strong anti-S. aureus agent. Finally, the antibacterial mechanism was analyzed, with flow cytometric analysis revealing that IG1 treatment resulted in a time-dependent decrease in the DNA content of S. aureus. Transmission electron microscopy (TEM) analysis showed that very few dividing cells could be found and the cell wall was damaged in the field of IG1-treated cells. These results indicate that IG1 is a potential new antibacterial agent against S. aureus, including MRSA.

Global financial systems are increasingly interconnected, and risks can spread more easily, potentially causing systemic risks. Research on systemic risk based on multi-layer financial networks is relatively scarce, and studies usually focus on only one type of risk. This paper develops a model of the multi-layer financial network system based on three types of links: firm-bank credit, asset-bank portfolio, and interbank lending, which simulates systemic risk under three risk sources: firm credit default, asset depreciation, and bank bankruptcy. The impact of the multi-layer financial network structure, default risk threshold, and bank asset allocation strategy is further explored. It has been shown that the larger the risk shock, the greater the systemic risk under different risk sources, and the risk propagation cycle tends to rise and then decline. As centralized nodes in the multi-layer financial network system, bank nodes may play both blocking and propagation roles under different risk sources. Furthermore, the multi-layer financial network system is most susceptible to bank bankruptcy risk, followed by firm credit default risk. Further research indicates that increasing the average degree of firms in the bank–firm credit network, the density of the bank-asset portfolio network, and the bank capital adequacy ratio all contribute to reducing systemic risk under the three risk sources. Additionally, the more assets a bank holds in a single market, the more vulnerable it is to the risks associated with that market.