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Radix Phytolaccae (RP) has a long medicinal history and is commonly used to treat systemic edema and ascites in Asia. Although RP is known to cause nephrotoxicity, the role of its main constituent, Esculentoside A (EsA), in nephrotoxicity remains undetermined. We used kidney organoids derived from human inducible pluripotent stem cells (iPSCs) to model EsA nephrotoxicity accurately. Kidney organoids were differentiated and treated with EsA at doses of 0, 15, 30, or 60 μM for 48 h. The in vitro model was compared to a mouse model of EsA nephrotoxicity (intraperitoneally injected, 25 mg·kg

The objective of this study was to describe and classify common variations and compensation mechanisms in the sagittal alignment of the spine with lumbar degenerative disease.A total of 230 patients over 18 years old who underwent whole-spine X-rays to evaluate lower back pain were enrolled in this study. C7 slope, pelvic tilt (PT), sacral slope (SS), pelvic incidence (PI), thoracic kyphosis (TK), lumbar lordosis (LL), cervical lordosis (CL), thoracolumbar kyphosis (TLK), and sagittal vertical axis (SVA) were measured. Patients were divided into Group A (balance without compensation), B (balance with compensation), C (unbalance with compensation), and D (unbalance without compensation) according to spinopelvic balance and thoracic compensation.Group A had the largest LL, smallest PT, largest SS, and best clinical parameters of the four groups (p 0.001, p 0.001, p 0.001, p 0.001). The age increased gradually from Group B to Group D. Group B had an increased TK compared with Group A (p 0.001). Group C had an increased TK compared with Group A (p 0.001). Group D had an increased C7 slope compared with Group A (p = 0.022).This classification is shown four different regional and global alignments of the spine. Compensation took place to keep the balance of the spine. Classification types were consistent with age, compensation abilities, and clinical parameters. This classification potentially represents a valuable tool for comprehensive analysis of lumbar degenerative before surgical treatment considering sagittal balance.

To assess the impact of childhood socioeconomic disadvantage (SED) on the risks of depression and physical multimorbidity in later life and to explore whether depression mediates the association between childhood SED and physical multimorbidity.Data on 8214 adults from the China Health and Retirement Longitudinal Study were analyzed. The mean (SD) age of the study population was 57.0 (8.0) years at baseline (2011) and 51.9 % were females. Multivariable logistic regressions were used to examine the associations of childhood SED (indexed by food insecurity, highest education level of parents, and self-perceived household financial situation, and scored 0-3) with later-life depression (scored ≥10 on the 10-item Center for Epidemiologic Studies Depression Scale) and physical multimorbidity (having two or more doctor-diagnosed chronic conditions) assessed in the 2018 follow-up survey. Mediation analysis was conducted in the overall sample and further stratified by sex to estimate the degree to which the association between childhood SED and physical multimorbidity could be explained by baseline depression.Participants with a childhood SED score of 3 (i.e., the most disadvantaged) had 2.63 (95 % confidence interval [CI]: 1.91-3.63) times and 2.08 (95 % CI: 1.56-2.77) times higher odds of depression and physical multimorbidity respectively compared with those who had a score of 0 (i.e., the least disadvantaged). Depression mediated 20 % of the association between childhood SED and physical multimorbidity (36 % in females and 5 % in males).Childhood SED was associated with higher risks of depression and physical multimorbidity in later life, and the association of childhood SED with physical multimorbidity was mediated by depression, especially among females.

Although gender-related disparities in intermediate-term outcomes have been reported after transcatheter aortic valve implantation (TAVI), disparate predictors of mortality in men and women who underwent TAVI have not been well studied. This prospective institutional registry study included 297 consecutive patients (153 men, 144 women) who underwent transfemoral TAVI from December 2015 to June 2018 at an academic tertiary medical center. Baseline and clinical characteristics, procedural data, and clinical outcomes at 1 year were recorded. Mortality rates at 1 year were 11.1% and 20.3% in women and men, respectively (p = 0.033). Risk-adjusted mortality was significantly higher in men who underwent TAVI than in women (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.24 to 4.87, p = 0.010). Gender-specific risk-adjusted predictors of 1-year mortality post-TAVI included the presence of atrial fibrillation (OR 4.20, 95% CI 1.31 to 13.46, p = 0.016) and peripheral artery disease (OR 4.64, 95% CI 1.04 to 20.71, p = 0.044) in women and presence of chronic obstructive pulmonary disease (OR 3.14, 95% CI 1.13 to 8.72, p = 0.029), higher serum creatinine (OR 1.57, 95% CI 1.15 to 2.15, p = 0.004), and lower body mass index (OR 0.88, 95% CI 0.80 to 0.97, p = 0.008) in men. In this prospective institutional registry of adults who underwent TAVI, risk-adjusted 1-year mortality is significantly lower in women, and disparate predictors of risk-adjusted 1-year mortality exist in men and women.

We describe a novel phenotype by which PLCε deficiency predisposes to aortic valve insufficiency and ascending aortic aneurysm, dissection, and sudden death in the setting of ANG II-mediated hypertension. We demonstrate PLCE1 variants in patients with type A aortic dissection and aortic insufficiency, suggesting that PLCE1 may also play a role in human aortic disease. This finding is of very high significance because it has not been previously demonstrated that PLCε directly mediates aortic dissection.

Polycystic ovary syndrome (PCOS) is a complicated endocrinopathy affecting women at reproductive age. Increasing evidence has shown the anti-PCOS effect of electroacupuncture (EA), a modified approach of traditional Chinese medical therapy "acupuncture". However, the underlying mechanism of EA-alleviated PCOS waits further explored. In this study, experimental PCOS were induced in rats by dehydroepiandrosterone (DHEA) injection. Testosterone (T)-induced human ovarian granulosa cell (GC) line KGN was used to mimic PCOS in vitro. EA significantly alleviated histological changes and hormone disruption in PCOS rats. Besides, EA inhibited cell apoptosis, autophagy and the activation of endoplasmic reticulum (ER) stress-related PERK/eIF2α/ATF4/CHOP signaling in ovaries of PCOS rats. More interestingly, intermedin (IMD), a member of calcitonin gene-related peptide (CGRP), was evidently up-regulated in ovarian GCs after EA treatment, and its main bioactive form IMD

Alzheimer's disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn

Background: Exercise is an effective nonpharmacological strategy to alleviate diabetic cardiomyopathy (DCM) through poorly defined mechanisms. FGF21 (fibroblast growth factor 21), a peptide hormone with pleiotropic benefits on cardiometabolic homeostasis, has been identified as an exercise responsive factor. This study aims to investigate whether FGF21 signaling mediates the benefits of exercise on DCM, and if so, to elucidate the underlying mechanisms. Methods: The global or hepatocyte-specific FGF21 knockout mice, cardiomyocyte-selective β-klotho (the obligatory co-receptor for FGF21) knockout mice, and their wild-type littermates were subjected to high-fat diet feeding and injection of streptozotocin to induce DCM, followed by a 6-week exercise intervention and assessment of cardiac functions. Cardiac mitochondrial structure and function were assessed by electron microscopy, enzymatic assays, and measurements of fatty acid oxidation and ATP production. Human induced pluripotent stem cell–derived cardiomyocytes were used to investigate the receptor and postreceptor signaling pathways conferring the protective effects of FGF21 against toxic lipids-induced mitochondrial dysfunction. Results: Treadmill exercise markedly induced cardiac expression of β-klotho and significantly attenuated diabetes-induced cardiac dysfunction in wild-type mice, accompanied by reduced mitochondrial damage and increased activities of mitochondrial enzymes in hearts. However, such cardioprotective benefits of exercise were largely abrogated in mice with global or hepatocyte-selective ablation of FGF21, or cardiomyocyte-specific deletion of β-klotho. Mechanistically, exercise enhanced the cardiac actions of FGF21 to induce the expression of the mitochondrial deacetylase SIRT3 by AMPK-evoked phosphorylation of FOXO3, thereby reversing diabetes-induced hyperacetylation and functional impairments of a cluster of mitochondrial enzymes. FGF21 prevented toxic lipids-induced mitochondrial dysfunction and oxidative stress by induction of the AMPK/FOXO3/SIRT3 signaling axis in human induced pluripotent stem cell–derived cardiomyocytes. Adeno-associated virus-mediated restoration of cardiac SIRT3 expression was sufficient to restore the responsiveness of diabetic FGF21 knockout mice to exercise in amelioration of mitochondrial dysfunction and DCM. Conclusions: The FGF21-SIRT3 axis mediates the protective effects of exercise against DCM by preserving mitochondrial integrity and represents a potential therapeutic target for DCM. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03240978.

Microplastics (MPs) can enter plants through the foliar pathway and are potential hazards to ecosystems and human health. However, studies related to the molecular mechanisms underlying the impact of foliar exposure to differently charged MPs to leafy vegetables are limited. Because the surfaces of MPs in the environment are often charged, we explored the uptake pathways, accumulation concentration of MPs, physiological responses, and molecular mechanisms of lettuce foliarly exposed to MPs carrying positive (MP

Background Surgical treatment of severe thoracolumbar kyphosis (TLK) secondary to late osteoporotic vertebral compression fracture (OVCF) presents several challenges to spine surgeons. Proper selection of distal fusion level is an important issue in surgical planning to decrease the likelihood of distal mechanical complications. This study was designed to compare the clinical and radiographic outcomes in elderly patients suffering from severe TLK related with late OVCF between different distal fusion strategies and to recommend a superior distal fusion level for these patients. Methods A total of 57 consecutive subjects with a minimum follow-up of two years were retrospectively reviewed. TLK was defined as the hyperkyphosis with an apex below T10. Severe TLK was defined as the Cobb angle of kyphosis ≥60°. Patients fused to sagittal stable vertebra (SSV) were assigned to Group SSV, while those fused to the vertebra above and below SSV were assigned to Groups SSV- and SSV+, respectively. Bone cement was used to enhance pedicle screw fixation. Clinical and radiographic results were collected and compared between different groups. Results Deformity corrections and living quality improvements at the latest follow-up were superior in Group SSV than Group SSV- with shorter fusion levels, while to the equal extent with Group SSV+ with longer fusion levels. 7 cases of distal complications were observed in Group SSV-. Negatively balanced lowest instrumented vertebra was revealed to be the independent factor predicting distal complications. Patients’ satisfaction of their surgical management was greater in Group SSV than Group SSV- (83.2 ± 4.4% vs. 70.5 ± 10.9%, P = 0.024), while comparable with Groups SSV + SSV+ (84.8 ± 5.7%). Conclusions Fusion to SSV with cement-augmented pedicle screws could limit the development of distal junctional mechanical complications after surgical treatment for severe TLK secondary to late OVCF in elderly patients, while achieves satisfactory deformity correction with the preservation of necessary lumbar motility.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system adapted from bacteria is a programmable nuclease-based genome editing tool. The long-lasting effect of gene silencing or correction is beneficial in cancer treatment. Considering the need to broaden the practical application of this technology, highly efficient non-viral vectors are urgently required. We prepared a multifunctional non-viral vector that could actively target tumor cells and deliver CRISPR/Cas9 plasmids into nuclei of cancer cells. Protamine sulfate (PS) which contains nuclear localization sequence was utilized to condense plasmid DNA and facilitate nuclei-targeted delivery. Liposome-coated protein/DNA complex avoided the degradation of nuclease in blood circulation. The obtained PS@Lip/pCas9 was further modified with distearoyl phosphoethanolamine-polyethylene glycol-hyaluronic acid (HA) to endow the vector ability to actively target tumor cell. Results suggested that PS@HA-Lip could deliver CRISPR/Cas9 plasmids into nuclei of tumor cells and induce genome editing effect. With the disruption of MTH1 (mutT homolog1) gene, the growth of non-small cell lung cancer was inhibited. Moreover, cell apoptosis in tumor tissue was promoted, and liver metastasis of non-small cell lung cancer (NSCLC) was reduced. Our study has provided a therapeutic strategy targeting MTH1 gene for NSCLC therapy. STATEMENT OF SIGNIFICANCE: CRISPR/Cas9 as a powerful tool for genome editing has drawn much attention. The long-lasting effect possesses unique advantage in cancer treatment. Non-viral vectors have high loading capacity, high safety and low immunogenicity, playing an important role in CRISPR/Cas9 delivery. In our study, a multifunctional non-viral vector for the efficient delivery of CRISPR/Cas9 plasmid was constructed. With the active targeting ligand and nuclei-targeting component, the cargo was efficiently delivered into cell nuclei and exerted genome editing effect. By using this vector, we successfully inhibited the growth and induced the apoptosis of non-small cell lung cancer by disrupting MTH1 expression with good safety. Our work provided an efficient non-vial vector for CRISPR/Cas9 delivery and explored the possibility for cancer treatment.

Photothermal and photodynamic therapies (PTT/PDT) have been widely accepted as noninvasive therapeutic methods for cancer treatment. However, tumor hypoxia and insufficient delivery of photoactive compounds to cancer cells can reduce the efficacy of phototherapy. Herein, we first synthesized thiolated hyaluronic acid (THA) and then conjugated it with catalase (CAT) onto chlorin e6 (Ce6)-adsorbed small gold nanorods (Ce6@sAuNRs) with near-infrared (NIR)/visible light activated photothermal/photodynamic effects. The conjugation of THA and CAT on Ce6@sAuNRs resulted in a red-shift of the longitudinal LSPR absorption band of sAuNRs up to 1000 nm and maintained the excellent enzymatic activity of catalase. Modification of Ce6@sAuNRs with THA resulted in efficient internalization of the nanocomposite into MCF-7/ADR multidrug-resistant (MDR) breast cancer cells (CD44+), thereby significantly enhancing the intracellular accumulation of the photosensitizer Ce6. CAT endows Ce6@sAuNRs with self-supporting oxygen production, which enables them to efficiently generate singlet oxygen (

Background It is challenging to detect pressure injuries at an early stage of their development. Objectives To assess the ability of an infrared thermography (IRT)-based model, constructed using a convolution neural network, to reliably detect pressure injuries. Methods A prospective cohort study compared validity in patients with pressure injury (n = 58) and without pressure injury (n = 205) using different methods. Each patient was followed up for 10 days. Results The optimal cut-off values of the IRT-based model were 0·53 for identifying tissue damage 1 day before visual detection of pressure injury and 0·88 for pressure injury detection on the day visual detection is possible. Kaplan–Meier curves and Cox proportional hazard regression model analysis showed that the risk of pressure injury increased 13-fold 1 day before visual detection with a cut-off value higher than 0·53 [hazard ratio (HR) 13·04, 95% confidence interval (CI) 6·32–26·91; P < 0·001]. The ability of the IRT-based model to detect pressure injuries [area under the receiver operating characteristic curve (AUC)lag 0 days, 0·98, 95% CI 0·95–1·00] was better than that of other methods. Conclusions The IRT-based model is a useful and reliable method for clinical dermatologists and nurses to detect pressure injuries. It can objectively and accurately detect pressure injuries 1 day before visual detection and is therefore able to guide prevention earlier than would otherwise be possible. What is already known about this topic? Detection of pressure injuries at an early stage is challenging.Infrared thermography can be used for the physiological and anatomical evaluation of subcutaneous tissue abnormalities.A convolutional neural network is increasingly used in medical imaging analysis. What does this study add? The optimal cut-off values of the IRT-based model were 0·53 for identifying tissue damage 1 day before visual detection of pressure injury and 0·88 for pressure injury detection on the day visual detection is possible.Infrared thermography-based models can be used by clinical dermatologists and nurses to detect pressure injuries at an early stage objectively and accurately.

Echinococcosis is a foodborne parasitic zoonosis caused by the larvae of

In this study, an adipic acid dihydrazide (ADH)/ tannic acid (TA)-grafted hyaluronic acid (HA)-based multifunctional hydrogel was synthesized through a spontaneous amino-yne click reaction and used to promote the improved healing of infected diabetic wounds. This hydrogel exhibited a range of beneficial properties such as tunable gelation time, adjustable mechanical properties, pH-sensitive response characteristics, excellent injectability, the ability to readily adhere to tissue, and ultra-intimate contact capabilities. Following the encapsulation of ultrasmall Ag nanoclusters (AgNCs) and deferoxamine loaded polydopamine/ hollow mesoporous manganese dioxide (PHMD, PDA/H-mMnO

The mortalities of hepatobiliary malignancies are high. With the failure of conventional chemotherapy and unsatisfactory outcome of molecular targeted drugs, immune-based therapy has become a new focus of research in hepatobiliary cancers treatment.We performed a PubMed search with relevant articles published up to May 2022 and the following keywords: cellular immunotherapy, hepatobiliary cancer, antigen receptor T cell therapy, and receptor-engineered T cell. Information of clinical trials was obtained from https://clinicaltrials.gov/.Cell therapies for hepatobiliary malignancies are at early stage of development. The current review showed that cellular therapies are safe and feasible in patients. These findings provide an important platform for future lager scale clinical trials on immunotherapy in patients with hepatobiliary malignancies.With the continuous advances of cellular immunotherapy, the combination of cellular immunotherapy with surgery, chemotherapy and radiotherapy will be new therapeutic strategies for patients with hepatobiliary cancer.

Microfluidic paper-based analytical devices (μPADs) are emerging as powerful analytical platforms in clinical diagnostics, food safety, and environmental protection because of their low cost and favorable substrate properties for biosensing. However, the existing top-down fabrication methods of paper-based chips suffer from low resolution (200 μm). Additionally, papers have limitations in their physical properties (e.g., thickness, transmittance, and mechanical flexibility). Here, we demonstrate a bottom-up approach for the rapid fabrication of heterogeneously controlled paper-based chip arrays. We simply print a wax-patterned microchip with wettability contrasts, enabling automatic and selective assembly of cellulose microfibers to construct predefined paper-based microchip arrays with controllable thickness. This paper-based microchip printing technology is feasible for various substrate materials ranging from inorganic glass to organic polymers, providing a versatile platform for the full range of applications including transparent devices and flexible health monitoring. Our bottom-up printing technology using cellulose microfibers as the starting material provides a lateral resolution down to 42 ± 3 μm and achieves the narrowest channel barrier down to 33 ± 2 μm. As a proof-of-concept demonstration, a flexible paper-based glucose monitor is built for human health care, requiring only 0.3 μL of sample for testing.

Emergence agitation is a common paediatric complication after inhalational anaesthesia. Intranasal dexmedetomidine can prevent emergence agitation effectively, but the optimal dose is uncertain.The aim of our study was to investigate the 95% effective dose (ED 95 ) of intranasal dexmedetomidine for the prevention of emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery.A prospective, randomised, placebo-controlled, double-blind, clinical trial.The study was conducted in Guangzhou Women and Children's Medical Center in China from August 2017 to December 2018.Three hundred and eighteen children scheduled for ambulatory surgery were enrolled into two age groups of less than 3 years and at least 3 years.The children in each age group were randomised into five equal subgroups to receive either intranasal dexmedetomidine 0.5, 1.0, 1.5 or 2.0 μg kg -1 (Groups D 0.5 , D 1.0 , D 1.5 and D 2.0 ), or intranasal isotonic saline (group C) after induction.The primary outcome was the ED 95 dose of intranasal dexmedetomidine for preventing emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery.The incidences of emergence agitation for Groups C, D 0.5 , D 1.0 , D 1.5 and D 2.0 were 63, 40, 23, 13 and 3% in children less than 3 years, and 43, 27, 17, 7 and 3% in children at least 3 years. The ED 95 of intranasal dexmedetomidine for preventing emergence agitation was 1.99 μg kg -1 [95% confidence interval (CI), 1.83 to 3.80 μg kg -1 ] in children less than 3 years, and 1.78 μg kg -1 (95% CI, 0.93 to 4.29 μg kg -1 ) in children at least 3 years. LMA removal time for groups D 1.5 and D 2.0 was 9.6 ± 2.2 and 9.7 ± 2.5 min, respectively, for children less than 3 years, and 9.4 ± 2.0 and 9.9 ± 2.7 min in children at least 3 years, respectively. Length of stay in the postanaesthesia care unit for Groups D 1.5 and D 2.0 was 34.3 ± 9.6 and 37.1 ± 11.2 min, respectively, in children less than 3 years, and 34.7 ± 10.2 and 37.3 ± 8.3 min in children at least 3 years, respectively. These times were longer in the D 1.5 and D 2.0 subgroups than in the control subgroup in the two age groups of less than 3 years and at least 3 years, respectively: 7.2 ± 1.9 min in children less than 3 years and 7.3 ± 2.5 min in children at least 3 years for LMA removal time, 22.2 ± 7.9 min in children less than 3 years and 22.0 ± 7.7 min in children at least 3 years for PACU stay time in control subgroup, respectively ( P 0.05).Intranasal dexmedetomidine prevented emergence agitation after paediatric surgery in a dose-dependent manner. The optimal dose of intranasal dexmedetomidine for preventing emergence agitation was higher in younger children.chictr.org.cn: ChiCTR-IOR-17012415.

Patients with anaplastic thyroid cancer (ATC) have a very poor prognosis. Immunotherapy is a potential treatment, while the current outcome is limited which may be due to the complicated tumor microenvironment (TME). Tumor associated macrophages (TAMs) is the most abundant cell in the TME of ATC. We aimed to clarify the novel indicators based on TAM in ATC.Transcriptome files were downloaded from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis, cox regression, support vector machine, and random forest were utilized to identify TAM-related prognostic genes. Consensus clustering and principal component analysis were performed for integrated analysis. Moreover, external validation (Fudan University Shanghai Cancer Center cohort) was conducted in 23 ATC samples via immunohistochemistry.ATC patients with an abundance of TAMs had a poorer prognosis. Four TAM related genes (FZD6, RBBP8, PREX1, HSD3B7) were identified and a TAM-related prognostic index (TAMRPI) was constructed with high area under the curve (AUC). Next, high TAMRPI was related to the higher level of TAM infiltration and upregulation of several pathways, such as E2F targets, IL6-JAK-STAT3, and G2M checkpoint. Immune checkpoint TIM-3 and CSF1R were positively associated with TAMRPI, and dysfunction of T cells was increased in high TAMRPI subset. Moreover, in the external validation of protein level, strong expression of TAM related genes was related to poorer prognosis, which was further supported by time-dependent AUC analysis.TAM is negatively correlated to the prognosis of ATC. FZD6, RBBP8, PREX1, and HSD3B7 are potential biomarkers of ATC.

This study assessed the cross-sectional associations of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) with hepatic steatosis in the National Health and Nutrition Examination Survey.Diet was measured using the 24-hour recalls. Hepatic steatosis was defined by vibration-controlled transient elastography. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression. Substitution analysis was performed using the leave-one-out model.Participants with higher adherence scores (comparing extreme tertiles) for an overall (OR = 0.76, 95% CI: 0.61-0.96, psubtrend/sub = 0.049) or a healthful LCD (OR = 0.61, 95% CI: 0.43-0.87, psubtrend/sub lt; 0.001) exhibited lower odds of steatosis. Replacing 5% of the energy from carbohydrates with total fat and protein (OR = 0.91, 95% CI: 0.83-0.99) or unsaturated fat and plant protein (OR = 0.89, 95% CI: 0.84-0.94) was associated with lower steatosis prevalence. High overall (OR = 1.65, 95% CI: 1.13-2.40, psubtrend/sub = 0.006) or unhealthful (OR = 1.41, 95% CI: 1.10-1.80, psubtrend/sub lt; 0.001) LFD scores were associated with increased likelihood of steatosis.These findings suggest that the associations between LCDs and LFDs and steatosis may depend on the quality and food sources of the macronutrients.

Context The optimal timing to performing thyroid surgery following a diagnosis of papillary thyroid cancer (PTC) has yet to be fully defined. Objective We aimed to examine if a delayed surgery may worsen the clinical outcome of PTC patients with intermediate- to high-risk of recurrence. Methods All consecutive PTC patients with intermediate- to high-risk of recurrence who underwent total thyroidectomy and radioactive iodine (RAI) ablation at 3 tertiary hospitals in southwest China were retrospectively included. Excellent response at 1-year follow-up after initial therapy was defined as no clinical, imaging, or biochemical evidence of PTC. Association of the timing of surgery and excellent response rates. Results The study included 871 patients. The median time interval between PTC diagnosis and surgery was 2 months (range, 1-87 months). Patients were divided according to the timing of surgery, < 6 months (group A, 624/871 [71.6%]), ≥ 6 to 11 months (group B, 123/871 [14.1%]), or ≥ 12 months (group C, 124/871 [14.2%]). One year after initial therapy, 64.7%, 71.5%, and 66.1% of patients in groups A, B, and C, respectively, achieved excellent response (P = 0.27). The lack of impact of surgery timing was observed across intermediate- to high-risk classifications and all T stage categories. These findings did not change when we separately analyzed the groups according to RAI dose (intermediate-dose group: ≤ 3.7 GBq [n = 654], and high-activity group: 5.5 GBq [n = 217]) further subdivided according to the timing of surgery. Conclusion Timing of surgery does not seem to affect short-term disease outcomes in intermediate- to high-risk PTC patients. Further research is necessary to assess the impact of delayed surgery on long-term prognosis.

Interferon (IFN)-induced protein 35 (IFI35, also known as IFP35), a member of IFN induced genes (ISGs), participates in virus infection, cancer progression and the chronic inflammatory diseases. However, its roles during fish nodavirus infection still remained largely unknown. In the present study, a homolog of IFI35 from orange spotted grouper (Epinephelus coioides) (EcIFI35) was cloned and characterized. The open reading frame of EcIFI35 was composed of 1,128 bp, and encoded a 375 amino acid polypeptide, which contained two conserved N-myc-interactor (Nmi)/IFP35 domains (NIDs). Homology analysis indicated that EcIFI35 shared 95.73% and 31.96% identity with homologs of giant grouper (E. lanceolatus) and human (Homo sapiens), respectively. The transcription of EcIFI35 was significantly up-regulated in grouper spleen (GS) cells after challenged with red-spotted grouper nervous necrosis virus (RGNNV), polyinosinic:polycytidylic acid [poly(I:C)] or lipopolysaccharide (LPS). The subcellular localization analysis showed that EcIFI35 encoded a cytoplasmic protein. The ectopic expression of EcIFI35 inhibited RGNNV replication by reducing viral genes transcription and protein synthesis. Co-immunoprecipitation (Co-IP) assay demonstrated that EcIFI35 interacted with RGNNV coat protein (CP), and partly co-localized with CP. EcIFI35 overexpression promoted the expression of IFN-related molecules and pro-inflammatory factors, including IFN regulatory factor 7 (IRF7), mitochondrial antiviral signaling protein (MAVS) and myxovirus resistance gene I (MxI), nuclear factor κB (NF-κB), interleukin 6 (IL-6) and IL-8. Together, our results revealed that EcIFI35 interacted with CP and inhibited fish nodavirus replication through positively regulated host innate immune response.

Stem cell treatment is vital for recovery from traumatic brain injury (TBI). However, severe TBI usually leads to excessive inflammation and neuroinhibitory factors in the injured brain, resulting in poor neural cell survival and uncontrolled formation of glial scars. In this study, a bioorthogonal microenvironment was constructed on biodegradable poly(lactide-co-glycolide) (PLGA) microcarriers through immobilization of mussel-inspired bioorthogonal 3,4-dihydroxyphenylalanine-containing recombinant nerve growth factor (DOPA-NGF) and human umbilical cord mesenchymal stem cells (hUMSCs) for minimally invasive therapy of TBI. Cell culture and RNA-seq analysis revealed enhanced extracellular matrix (ECM) secretion and viability of hUMSCs on PLGA microcarriers compared to 2D culture. Immobilized DOPA-NGF further promoted adhesion, proliferation, and gene expression in RSC96 neurotrophic cells and hUMSCs. Specifically, the neurotrophin receptor of NT-3 (NTRK3) in hUMSCs was activated by DOPA-NGF, leading to MYC transcription and paracrine enhancement to build an adjustable biomimetic microenvironment. After transplantation of microunits in animal models, the motor and learning-memory ability of TBI mice were improved through rollbacks of overactivated inflammatory reaction regulation, neuronal death, and glial scar formation after injury. This was attributed to the paracrine enhancement of hUMSCs activated by the DOPA-NGF. Our study provides a neural regenerative microenvironment-based therapeutic strategy to advance the effects of transplanted hUMSCs in cell-based regenerative medicine for TBI therapy. STATEMENT OF SIGNIFICANCE: Extensive studies have demonstrated the importance of the microenvironment for posttraumatic brain injury recovery. However, an efficient method that can mimic the neural regenerative microenvironment to strengthen stem cell therapy and brain injury recovery is still absent. In this study, the minimally invasive transplantation of DOPA-NGF immobilized biodegradable microcarriers with mesenchymal stem cells was found to be an effective method for regeneration of injured brain. Moreover, transcriptome analysis revealed that neurotrophin receptor of NT-3 (NTRK3) was activated by DOPA-NGF for MYC transcription and paracrine enhancement to build a kind of adjustable biomimetic microenvironment for brain injury therapy. This study provides a neural regenerative microenvironment-based therapeutic strategy to advance the transplanted hUMSCs in cell-based regenerative medicine for neural recovery.

Prescribing a ketogenic diet (KD) is a century-old dietary intervention mainly used in the context of intractable epilepsy. The classic KD and its variants regained popularity in recent decades, and they are considered potentially beneficial in a variety of neurological conditions other than epilepsy. Many patients with multiple sclerosis (MS) have attempted diet modification for better control of their disease, although evidence thus far remains insufficient to recommend a specific diet for these patients. The results of 3 pilot clinical trials of KD therapy for MS, as well as several related studies, have been reported in recent years. The preliminary findings suggest that KD is safe, feasible, and potentially neuroprotective and disease-modifying for patients with MS. Research on corresponding rodent models has also lent support to the efficacy of KD in the prevention and treatment of experimental autoimmune encephalomyelitis and toxin-induced inflammatory demyelinating conditions in the brain. Furthermore, the animal studies have yielded mechanistic insights into the molecular mechanisms of KD action in relevant situations, paving the way for precision nutrition. Herein we review and synthesize recent advances and also identify unresolved issues, such as the roles of adipokines and gut microbiota, in this field. Hopefully this panoramic view of current understanding can inform future research directions and clinical practice with regard to KD in MS and related conditions.

Background: National and international experts have been attempting to find diagnostic tools for the early identification of symptoms to facilitate early identification and intervention of the disease. Objective: Detection of urine Alzheimer-associated neuronal thread protein (AD7c-NTP) and serum 25-hydroxyvitamin D (25(OH)D) in the diagnosis of Alzheimer’s disease (AD). Methods: Subjects aged >50 years who underwent a physical examination at the Taihu Sanatorium of Jiangsu Province, had no clinical evidence of AD-related issues, and had normal Mini-Mental State Exam and Montreal Cognitive Assessment scores were enrolled in the present study. There were 35 males and 15 females, who were aged 51–91 years. Urine AD7c-NTP levels and serum 25(OH)D concentrations were measured. Results: The Pearson correlation analysis revealed that the urine AD7c-NTP levels in these subjects were negatively correlated with the serum 25(OH)D concentrations (r = –0.460, p

The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility.The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD.A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification.In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively.Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

Anti-mitochondrial autoantibodies (AMAs) are highly specific for the diagnosis of primary biliary cholangitis (PBC) but are also occasionally found in other diseases. In the present study, we evaluated the incidence of and predictors for PBC development in AMA-positive patients with other liver or non-liver diseases at baseline. In this retrospective study, we screened patients who tested positive for AMA and/or anti-mitochondrial M2 antibody (AMA-M2) at Beijing Friendship Hospital, Capital Medical University, from October 2005 to January 2017. They were categorized by their diagnosis at the baseline as patients with PBC or non-PBC cases. We followed up on the non-PBC cases through telephone interviews and reviewing of medical records to obtain laboratory results and clinical outcomes. In total, 139 patients were AMA-positive but did not fulfill the diagnostic criteria of PBC at baseline, including 51 patients with non-PBC liver diseases and 88 cases with non-liver diseases. The titers of AMA-M2, alkaline phosphatase, gamma-glutamyl transpeptidase, and immunoglobulin M were significantly higher in patients with PBC compared to those with non-PBC liver diseases and non-liver diseases. After a median follow-up of 4.6 (interquartile range: 2.4-7.6) years, 4.3% (6 of 139) developed PBC, with an accumulative 5-year incidence rate of 4.2%. None of the patients with non-PBC liver diseases developed PBC, whereas the 5-year incidence rate of PBC was 7.8% among 88 patients with non-liver diseases. Lower alanine aminotransferase and higher immunoglobulin M were independent predictors for developing PBC. Conclusion: Our results suggest a low risk of developing PBC over time in AMA-positive patients with other liver and non-liver diseases.

Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD’s pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.

Opinion statementGastrointestinal stromal tumor (GIST), though rare, is the most common mesenchymal tumors of the gastrointestinal tract. KIT or PDGFRα mutation plays as an oncogenic driver in the majority of GISTs. Surgical resection is the only curative treatment for localized disease. The discovery of imatinib with promising anti-tumor effect and successive tyrosine kinase inhibitors (TKI), including second-line sunitinib and third-line regorafenib, revolutionized the management of advanced and metastatic GIST over the past two decades. Recently, ripretinib and avapritinib were approved for the fourth line setting and for PDGFRA exon 18-mutant GIST in first-line setting, respectively. Despite multi-line TKIs exerted ability of disease control, drug resistance remained an obstacle for preventing rapid disease progression. Experimental TKIs or novel therapeutic targets may further improve treatment efficacy. Immune checkpoint inhibitors such as anti-programmed cell death protein-1 (PD1) and anti-CTL-associated antigen 4 (CTLA-4) showed moderate response in early phase trials composed of heavily pretreated patients. KIT/PDGFRα wild-type GISTs are generally less sensitive to imatinib and late-line TKIs. Recent studies demonstrated that targeting fibroblast growth factor receptor signaling may be a potential target for the wild-type GISTs.

Pediatric HIV testing remains suboptimal. The OraQuick test [saliva-based test (SBT)] is validated in pediatric populations ≥18 months. Understanding caregiver and health care worker (HCW) acceptability of pediatric SBT is critical for implementation.A trained qualitative interviewer conducted 8 focus group discussions (FGDs): 4 with HCWs and 4 with caregivers of children seeking health services in western Kenya. FGDs explored acceptability of pediatric SBT and home- and facility-based SBT use. Two reviewers conducted consensus coding and thematic analyses of transcripts using Dedoose.Most HCWs but few caregivers had heard of SBT. Before seeing SBT instructions, both had concerns about potential HIV transmission through saliva, which were mostly alleviated after kit demonstration. Noted benefits of SBT included usability and avoiding finger pricks. Benefits of facility-based pediatric SBT included shorter client waiting and service time, higher testing coverage, and access to HCWs, while noted challenges included ensuring confidentiality. Benefits of caregivers using home-based SBT included convenience, privacy, decreased travel costs, increased testing, easier administration, and child comfort. Perceived challenges included not receiving counseling, disagreements with partners, child neglect, and negative emotional response to a positive test result. Overall, HCWs felt that SBT could be used for pediatric HIV testing but saw limited utility for caregivers performing SBT without an HCW present. Caregivers saw utility in home-based SBT but wanted easy access to counseling in case of a positive test result.SBT was generally acceptable to HCWs and caregivers and is a promising strategy to expand testing coverage.

Anthracyclines constitute the cornerstone of numerous chemotherapy regimens for various cancers. However, the clinical application of anthracyclines is significantly limited to their dose-dependent cardiotoxicity. A comprehensive understanding of the current status of anthracycline-induced cardiotoxicity is necessary for in-depth research and optimal clinical protocols. Bibliometric analysis is widely applied in depicting development trends and tracking frontiers of a specific field. The present study is aimed at revealing the status and trends of anthracycline-induced cardiotoxicity during the past two decades by employing bibliometric software including R-bibliometric, VOSviewer, and CiteSpace. A total of 3504 publications concerning anthracycline-induced cardiotoxicity from 2002 to 2021 were collected from the Web of Science Core Collection database. Results showed significant growth in annual yields from 90 records in 2002 to 304 papers in 2021. The United States was the most productive country with the strongest collaboration worldwide in the field. Charles University in the Czech Republic was the institution that contributed the most papers, while 7 of the top 10 productive institutions were from the United States. The United States Department of Health and Human Services and the National Institutes of Health are the two agencies that provide financial support for more than 50% of sponsored publications. The research categories of included publications mainly belong to Oncology and Cardiac Cardiovascular Systems. The Journal of Clinical Oncology had a comprehensive impact on this research field with the highest IF value and many publications. Simunek Tomas from Charles University contributed the most publications, while Lipshultz Steven E. from the State University of New York possessed the highest H -index. In addition, the future research frontiers of anthracycline-induced cardiotoxicity might include early detection, pharmacogenomics, molecular mechanism, and cardiooncology. The present bibliometric analysis may provide a valuable reference for researchers and practitioners in future research directions.

Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP.Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP.High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results.Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs.

Li et al delineate a novel technique for assessing measurable residual disease (MRD) by the assessment of isolated leukemia stem cells (LSCs). They report that assessment of MRD in LSCs provides a better prediction of outcome than standard multiparameter flow cytometry.

Recently, lactate has been considered as an alternative direct energy substance to glucose for tumor proliferation and metastasis. Meanwhile, mitochondria, as important energy-supplying organelles, are also closely related to tumor progression. Consequently, a new research direction for lactate comprises lactate deprivation coupled with mitochondria-targeted phototherapy to achieve a safer and more effective strategy against tumor metastasis. Herein, linoleic acid-conjugated hyaluronic acid (HL), disulfide bond-rich nanovehicle (mesoporous silica, MOS), mitochondria-targeted IR780 (M780) and lactate oxidase (LOD) are rationally designed as a specific-targeting metabolism nanomodulator (HL/MOS@M780LOD NPs), fulfilling the task of simultaneous depriving cells of lactate and damaging mitochondria to prevent tumor metastasis. Interestingly, M780-mediated photodynamic therapy (PDT) and LOD-mediated starvation therapy can effectively exacerbate the hypoxia state of tumor cells, thereby increasing the free iron levels to activate ferroptosis. On one hand, pyruvic acid and H

Whey protein (WP) can increase insulin secretion, produce an incretin effect, delay gastric emptying, and regulate appetite, resulting in improved glycemic control. We hypothesized that WP supplementation is associated with postprandial glycemia regulation in persons with type 2 diabetes mellitus (T2DM) and conducted a quantitative meta-analysis of randomized controlled trials (RCTs) to test this hypothesis. We searched PubMed, Embase, Cochrane Library, Scopus databases, and the ClinicalTrials.gov registry for relevant RCTs published before March 2022. We assessed the pooled effects using a random-effects model on glucose and insulin levels at 60 and 120 minutes, total glucagon-like peptide-1 (tGLP-1) at 30 and 60 minutes, and the incremental area under the curve (iAUC) of glucose, insulin, tGLP-1, and glucose-dependent insulinotropic polypeptide. Five RCTs involving 134 persons were included. Postprandial glycemia was significantly lower at 60 minutes (weighted mean difference: -2.67 mmol/L; 95% confidence interval, -3.62 to -1.72 mmol/L) and 120 minutes (-1.59 mmol/L; -2.91 to -0.28 mmol/L) in WP group than in placebo group. The iAUC of insulin was significantly higher in WP group (24.66 nmol/L × min, 1.65-47.66 nmol/L × min) than in placebo group. Although other results favored the WP group, differences between the groups were not statistically significant. The present study showed that premeal WP supplementation is beneficial for postprandial glycemia in persons with mild or well-controlled T2DM without substantial adverse effects. However, the level of certainty of current evidence is not high enough. Further larger and well-designed clinical trials are warranted for evaluating optimal dose and long-term effects of WP supplementation.

Background: Spinal muscular atrophy (SMA) is a common neuromuscular disorder, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Population-wide SMA screening to quantify copy number of SMN1 is recommended by multiple regions. SMN1 diagnostic assay with simplified procedure, high sensitivity and throughput is still needed.Methods: Real-Time PCR with High-Resolution Melting for the quantification of the SMN1 gene exon 7 copies and SMN1 gene exon 8 copies was established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals including SMA patients, suspected cases and the general population were analyzed by the real-time PCR. The results were compared with the gold standard test MPLA. Results: In this study, the homozygous deletions, heterozygous deletions were identified by Real-Time PCR with High-Resolution Melting method with an incidence of 10.18% and 2.42%, respectively. In addition, the R value distribution (P>0.05) among the 8 replicates and the coefficient of variation (CVConclusions: The qPCR based on High-Resolution Melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.

Etiologic associations between some modifiable factors (metabolic risk factors and lifestyle behaviors) and cardiovascular disease (CVD) remain unclear. To identify targets for CVD prevention, we evaluated the causal associations of these factors with coronary artery disease (CAD) and ischemic stroke using a two-sample Mendelian randomization (MR) method.Previously published genome-wide association studies (GWASs) for blood pressure (BP), glucose, lipids, overweight, smoking, alcohol intake, sedentariness, and education were used to identify instruments for 15 modifiable factors. We extracted effects of the genetic variants used as instruments for the exposures on coronary artery disease (CAD) and ischemic stroke from large GWASs (N = 60 801 cases/123 504 controls for CAD and N = 40 585 cases/406 111 controls for ischemic stroke). Genetically predicted hypertension (CAD: OR, 5.19 [95% CI, 4.21-6.41]; ischemic stroke: OR, 4.92 [4.12-5.86]), systolic BP (CAD: OR, 1.03 [1.03-1.04]; ischemic stroke: OR, 1.03 [1.03-1.03]), diastolic BP (CAD: OR, 1.05 [1.05-1.06]; ischemic stroke: OR, 1.05 [1.04-1.05]), type 2 diabetes (CAD: OR, 1.11 [1.08-1.15]; ischemic stroke: OR, 1.07 [1.04-1.10]), smoking initiation (CAD: OR, 1.26 [1.18-1.35]; ischemic stroke: OR, 1.24 [1.16-1.33]), educational attainment (CAD: OR, 0.62 [0.58-0.66]; ischemic stroke: OR, 0.68 [0.63-0.72]), low-density lipoprotein cholesterol (CAD: OR, 1.55 [1.41-1.71]), high-density lipoprotein cholesterol (CAD: OR, 0.82 [0.74-0.91]), triglycerides (CAD: OR, 1.29 [1.14-1.45]), body mass index (CAD: OR, 1.25 [1.19-1.32]), and alcohol dependence (OR, 1.04 [1.03-1.06]) were causally related to CVD.This systematic MR study identified 11 modifiable factors as causal risk factors for CVD, indicating that these factors are important targets for preventing CVD.

Food additives are widespread in the human diet; however, their excessive intake can have an impact on the quality of health. This study evaluated food additives in bread and pasta products consumed by residents in various regions of Jilin Province, People's Republic of China, from 2019 to 2021. We collected samples of bread and six types of pasta products from farmers' markets and morning markets and used high-performance liquid chromatography, UV-visible spectrophotometry, and graphite furnace atomic absorption spectrometry to detect the content of the following food additives: sodium formaldehyde sulfoxylate, aluminum, and borate compounds. For 836 samples in total, we detected the presence of sodium formaldehyde sulfoxylate, aluminum, and borate compounds in excess rates reaching 3.5, 10, and 4.7%, respectively. Aluminum in fried breadsticks exceeded the standard by 40%. The results of this study can be used to assess the overall pass rate of bread and pasta products sold in Jilin Province and support the detection of possible food safety problems.

Yu Wang,1,&ast; Hanning Zha,1,&ast; Xiang Fang,2 Tianjiao Shen,1 Kunyun Pan,1 Jianping Zhang,1 Keqiang He,1 Sheng Wang,1 Liguo Hu1 1Department of Anesthesiology, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Anesthesiology, Hefei BOE Hospital, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sheng Wang; Liguo Hu, Email iamsheng2020@ustc.edu.cn; hulg@163.comObjective: The dose selection of ropivacaine for spinal anesthesia in clinical work mainly depends on the experience of the anesthesiologist. In this study, a prospective and modified up-down sequential allocation design was used to provide the optimal dose selection of ropivacaine for spinal anesthesia.Patients and methods: This study was divided into two stages, and a total of 164 elderly patients with elective hip fractures were included. In stage I, the dose of ropivacaine was selected using the up-down sequential method of height correction, and the 50% effective dose (ED50) and 95% effective dose (ED95) were obtained. A nomogram for predicting satisfactory anesthesia and a formula for predicting the optimal dose was also given in this stage. In stage II, the dose of ropivacaine was calculated by using the optimal dose prediction formula, so as to evaluate the efficacy and safety of the model.Results: The ED50 and ED95 of the stage I were 7.036 mg (95%CI 6.549– 7.585 mg) and 8.709 mg (95%CI 7.902– 14.275 mg), respectively. And provided a nomogram predicting satisfactory anesthesia with a C-index of 0.847 (95%CI 0.774– 0.92). The optimal dose prediction formula of ropivacaine was calculated, including variables for age, gender, height, and weight. This formula was found to be 90% efficient. It is worth mentioning that the incidence of direct transfer to the ward in the two stages was as high as 86.84% and 93.33%, respectively, and no patients were transferred to the ICU in stage II.Conclusion: The ED50 and ED95 of ropivacaine were 7.036 mg and 8.709 mg, respectively, and the nomograms are sufficiently accurate to predict satisfactory anesthesia. Beyond that, the dose prediction equation provided in this study has high efficacy and safety, and can guide the dose selection of spinal anesthesia in elderly patients with hip fracture in clinical practice.Clinical trials registration: ChiCTR2100046982Keywords: ropivacaine, dose selection, elder, spinal anesthesia, Hip fracture, sequential design

Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer worldwide, and treatment outcomes are still poor. Magnolol, a hydroxylated biphenyl isolated from Magnolia officinalis, was found to be effective against hepatocellular carcinoma via inactivating nuclear-factor-kappa B (NF-B) signaling. However, whether magnolol targets not only NF-B but also other factors in NSCLC and may contribute to the suppression of tumor progression is unclear.Cell viability, flow cytometry, and western blotting assays were used to identify the mechanism of magnolol action in human lung adenocarcinoma cell lines A549 and CL1-5-F4.Our results indicated that magnolol induced cytotoxicity through extrinsic/intrinsic apoptosis signaling and suppressed phosphorylation of signal transducer and activator of transcription 3 (STAT3)/NF-B and expression of their downstream proteins.Magnolol not only induced extrinsic and intrinsic apoptosis signaling but also inactivated STAT3/NF-B and attenuated their signaling of epithelial-mesenchymal transition and metastasis-related protein expression in NSCLC.

Amyloid-β peptide (Aβ) aggregation is one of the hallmarks of Alzheimer's disease (AD). Mutations in Aβ are associated with early onset familial AD, and the Arctic mutant E22G (Aβ

As the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to emerge, periodic vaccine booster immunization may become a normal policy. This study investigated the changes and factors associated with vaccination intentions in various epidemic situations, which can provide suggestions for the construction and modification of routine vaccination program strategies.Two cross-sectional online surveys were conducted in January and June of 2021. The willingness and confidence of the coronavirus disease 2019 (COVID-19) vaccination were measured following propensity score matching (PSM) treatment. The difference in the willingness for COVID-19 Vaccination in the two surveys was analyzed by single or multi-factor analyses.The willingness to accept the SARS-CoV-2 vaccine was higher in the second survey than that in the first survey (90.5% vs. 66.6%, p 0.001). Concerns about the vaccine's safety declined (71.0% vs. 47.6%, p 0.001), but concerns about the efficacy increased (22.4% vs. 30.9%, p 0.001). Confidence in the SARS-CoV-2 vaccine had an important impact on the increased uptake willingness (odds ratio = 3.19, 95% confidence interval: 2.23-4.58, p 0.001).There has been a significant increase in attitudes towards the SARS-CoV-2 vaccine which was associated with higher vaccine confidence. Vaccine effectiveness received more concerns from respondents rather than safety after nearly 6 months' utilization of the SARS-CoV-2 vaccine. It indicates that aggressive communication and timely disclosure of vaccine data can build vaccine confidence.

Nonsyndromic cleft lip with palate (nsCLP) is a common congenital malformation; however, early prenatal diagnosis is challenging and pathogenesis remains unclear. The purpose of this study was to determine the diagnostic potential of miRNAs in plasma-derived exosomes and whole plasma of pregnant women to identify nsCLP and an underlying mechanism. Combined RNA sequencing analysis was performed on samples from plasma exosomes and whole plasma of pregnant women carrying normal fetuses or fetuses with nsCLP in an ongoing birth cohort, in addition to lip samples from nsCLP fetuses and healthy controls. Eight let-7 cluster miRNAs (hsa-let-7a-3p, hsa-let-7a-5p, hsa-let-7c-5p, hsa-let-7d-3p, hsa-let-7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, and hsa-miR-98-5p) in plasma exosomes from pregnant women provided higher sensitivity/specificity for diagnosing fetal nsCLP than those in plasma. Area under the receiver operating characteristic curve value of the eight miRNAs from plasma exosomes was 0.992. Among them, hsa-let-7a-3p showed better diagnostic capability and was downregulated in nsCLP fetal lip tissues. Upstream and downstream target genes of hsa-let-7a-3p were screened and confirmed. Our work highlights the potential clinical application value of let-7 clusters in predicting nsCLP and associates as a new regulatory axis (EN2-LIN28A-hsa-let-7a-3p-HHIP-GLI2) with human nsCLP pathogenesis.

Bronchopulmonary dysplasia (BPD) represents a multifactorial chronic pulmonary pathology and a major factor causing premature illness and death. The therapeutic role of exosomes in BPD has been feverishly investigated. Meanwhile, the potential roles of exosomal circRNAs, lncRNAs, and mRNAs in umbilical cord blood (UCB) serum have not been studied. This study aimed to detect the expression profiles of circRNAs, lncRNAs, and mRNAs in UCB-derived exosomes of infants with BPD. Microarray analysis was performed to compare the RNA profiles of UCB-derived exosomes of a preterm newborn with (BPD group) and without (non-BPD, NBPD group) BPD. Then, circRNA/lncRNA–miRNA–mRNA co-expression networks were built to determine their association with BPD. In addition, cell counting kit-8 (CCK-8) assay was used to evaluate the proliferation of lipopolysaccharide (LPS)-induced human bronchial epithelial cells (BEAS-2B cells) and human umbilical vein endothelial cells (HUVECs). The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β in LPS-induced BEAS-2B cells and HUVECs were assessed through Western blot analysis. Then, quantitative reverse transcription–polymerase chain reaction assay was used to evaluate the expression levels of four differentially expressed circRNAs (hsa_circ_0086913, hsa_circ_0049170, hsa_circ_0087059, and hsa_circ_0065188) and two lncRNAs (small nucleolar RNA host gene 20 (SNHG20) and LINC00582) detected in LPS-induced BEAS-2B cells or HUVECs. A total of 317 circRNAs, 104 lncRNAs, and 135 mRNAs showed significant differential expression in UCB-derived exosomes of preterm infants with BPD compared with those with NBPD. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to examine differentially expressed exosomal circRNAs, lncRNAs, and mRNAs. The results showed that the GO terms and KEGG pathways mostly involving differentially expressed exosomal RNAs were closely associated with endothelial or epithelial cell development. In vitro, CCK-8 and Western blot assays revealed that LPS remarkably inhibited the viability and promoted inflammatory responses (TNF-α and IL-1β) of BEAS-2B cells or HUVECs. The expression levels of circRNAs hsa_circ_0049170 and hsa_circ_0087059 were upregulated in LPS-induced BEAS-2B cells; the expression level of hsa_circ_0086913 was upregulated and that of hsa_circ_0065188 was downregulated in LPS-induced HUVECs. Moreover, the expression level of lncRNA SNHG20 was upregulated and that of LINC00582 was downregulated in LPS-induced BEAS-2B cells. Further, 455 circRNA/lncRNA–miRNA–mRNA interaction networks were predicted, including hsa_circ_0086913/hsa-miR-103a-3p/transmembrane 4 L six family member 1 (TM4SF1) and lncRNA-SNHG20/hsa-miR-6720-5p/spermine synthase (SMS) networks, which may take part in BPD.Conclusion: This study provided a systematic perspective on UCB-derived exosomal circRNAs and lncRNAs and laid an important foundation for further investigating the potential biological functions of exosomal circRNAs and lncRNAs in BPD. What is Known:• BPD represents a multifactorial chronic pulmonary pathology and a major factor causing premature illness and death.• The therapeutic role of exosomes in BPD has been feverishly investigated, and exosomal RNAs were ignored. What is New:• The profiles of UCB-derived exosomal circRNAs, lncRNAs, and mRNAs were performed.• Several differentially expressed circRNAs and lncRNAs were identified in LPS-induced BEAS-2B cells and HUVECs.

Nonagenarians with community-acquired pneumonia (CAP) have a high mortality rate; however, appropriate tools for reliable severity assessment in this population are lacking. The current study aimed to evaluate the risk factors and establish a nomogram to predict in-hospital mortality of nonagenarians with CAP.In total, 304 patients aged ≥90 years who were admitted with CAP to Jiangsu Provincial People's Hospital and Jiangsu Provincial Hospital of Chinese Medicine between 2014 and 2020 were retrospectively analyzed. Clinical information, laboratory imaging results and pathogen detection were retrieved. Significant variables independently associated with CAP were identified by a logistic regression model, and a nomogram prediction model was constructed. The nomogram was compared with the widely used assessments: CURB-65, PSI and National Early Warning Score (NEWS) scores.Univariate and multivariate logistic regression analyses identified gender, blood urea nitrogen, C-reactive protein-to-albumin ratio, Charlson Comorbidity Index and systemic immune inflammation index as independent factors that affect the prognosis. We created a nomogram for CAP based on these risk factors. The nomogram had a bootstrapped concordance index of 0.796 and was well-calibrated in the decision analysis curve range of 0.1-0.98. The area under the curve was 0.796 (95% CI: 0.74-0.85), significantly higher than for CURB-65, PSI and NEWS scores (P 0.05).Our nomogram model can predict the outcome of hospitalized nonagenarians with CAP and guide clinicians to provide better treatment, leading to improved prognosis and reduced mortality. Geriatr Gerontol Int 2022; 22: 635-641.

The authors investigated the effectiveness of home-based transcutaneous electrical acupoint stimulation (TEAS) combined with lifestyle modification on blood pressure (BP) control and explored the feasibility of the trial design in this prospective, randomized controlled trial. The authors recruited individuals with high-normal BP who had a systolic blood pressure (SBP) of 120-139 mm Hg and a diastolic blood pressure (DBP) of 80-89 mm Hg, or both. Participants were randomly assigned to receive either lifestyle modification combined with TEAS four times weekly for 12 weeks at home (intervention group) or solely lifestyle modification (control group). The primary outcome was the change in mean SBP at week 12 from the baseline measurement. A total of 60 participants were randomized in a 1:1 ratio, and an intention-to-treat analysis was performed on all of the outcomes. The mean difference in the change in SBP for the intervention group (compared to the control) at week 12 was -3.85 mm Hg (95% CI: -7.58 to -.12; p = .043); for the DBP, the change was -2.27 mm Hg (95% CI: -5.76 to 1.23; p = .199). There was no difference in the proportion of progression to hypertension, quality of life, body mass index (BMI) or waist circumference. In addition, two participants reported TEAS-related adverse events. The authors found a reduction in SBP control in the pragmatic, home-based intervention by using TEAS combined with lifestyle modification in adults with high-normal BP. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR 1900024982) on August 6, 2019.

Magnetic resonance imaging-guided adaptive radiation therapy (MRIgART) greatly improves daily tumor localization and enables online replanning to obtain maximum dosimetric benefits. However, accurately predicting patient-specific electron density maps for adaptive radiation therapy planning remains a challenge. Therefore, this study proposes a personalized modeling framework for generating pseudo-computed tomography (pCT) in MRIgART.Eighty-three patients who received MRIgART were included and computed tomography (CT) simulations were performed on all the patients. Daily T2-weighted 1.5 T magnetic resonance imaging (MRI) was acquired using the Unity MR-linac for adaptive planning. Pairs of coregistered CT and daily MRI images of the randomly selected training set (68 patients) were inputted into a generative adversarial network to establish a population model. The personalized model for each patient in the test set (15 patients) was acquired using model fine-tuning, which adopted the pair of the deformable-registered CT and the first daily MRI to fine-tune the population model. The pCT quality was quantitatively evaluated in the second and the last fractions with 3 metrics: intensity accuracy using mean absolute error; anatomic structure similarity using dice similarity coefficient; and dosimetric consistency using gamma-passing rate.The image generation speed was 65 slices/s. For the last fractions, and for head-neck, thoracoabdominal, and pelvic cases, the average mean absolute errors were 76.8 HU versus 123.6 HU, 38.1 HU versus 52.0 HU, and 29.5 HU versus 39.7 HU, respectively. Furthermore, the average dice similarity coefficients of bone were 0.92 versus 0.80, 0.85 versus 0.73, and 0.94 versus 0.88; and the average gamma-passing rates (1%/1 mm) were 95.5% versus 84.7%, 97.7% versus 92.8%, and 95.5% versus 88.7%, for personalized versus population models, respectively. The results of the second fractions were similar.The proposed personalized modeling framework remarkably improved pCT quality for multiple treatment sites and was well suited for the MRIgART clinical setting.

The non-O1/non-O139 Vibrio cholerae caused outbreaks or sporadic cases of gastroenteritis that was rarely seen in good sanitary condition. It was described a case of systemic multiple organ lesions that worsened because of non-O1/non-O139 V. cholerae, suggesting that serogroups have a potential virulence in enhancing pathogenicity with patients with underlying diseases compared with a healthy population.Samples are identified by strain culture, polymerase chain reaction (PCR) virulence identification, and whole genome sequencing.A middle-aged man was diagnosed with cytotoxin-producing and nontoxin V. cholerae non-O1/non-O139 serogroups. Although lacking the CT toxin encoded by ctxAB gene, the pathogenesis of cholera relies on the synergistic action of many other genes, especially virulence genes.This case suggested that the laborers engaging in agricultural production are at potential risk of V. cholerae infection by exposure of open wounds to contaminated water . However, epidemiological investigation should focus on the objective cause of the change of working environment. Furthermore, common diseases can possibly enhance the virulence of non-O1/non-O139 serogroups by attacking the tight junction of small intestinal epithelial cells, further triggering bacteremia, a process that may lead to death within 48-72 hours, which requires great attention.