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Background Cervical spondylosis adversely affects life quality for its heavy disease burden. The report on the community-based prevalence and associated factors of cervical spondylosis is rare, especially in Chinese population. Whether prevention is needed and how to prevent it is not clear. This study aims to explore its prevalence and related lifestyle factors and provide evidence on prevention of cervical spondylosis. Methods A community-based multistage cross-sectional survey of six communities from the Chinese population was conducted. A face-to-face interview was conducted to obtain individual information, and prevalence was calculated. Single-factor analysis and multivariable logistic regressions were used to explore the associated factors in total and subgroup populations. Results A total of 3859 adults were analyzed. The prevalence of cervical spondylosis was 13.76%, although it differed significantly among the urban, suburban, and rural populations (13.07%, 15.97%, and 12.25%, respectively). Moreover, it was higher in females than in males (16.51% vs 10.49%). The prevalence among different age groups had an inverted U shape. The highest prevalence was in the age group from 45 to 60 years old. The associated factors differed by subgroups. There were positive associations between engaging in mental work, high housework intensity, and sleep duration of less than 7 h/day with cervical spondylosis. Going to work on foot was a negative factor of cervical spondylosis in the total population. For people aged less than 30 years, keeping the same work posture for 1–2.9 h/day was a special related factor. Exposure to vibration was an associated factor for females aged 45–60 years. Menopause was a special related factor for women. Conclusions Prevalence of cervical spondylosis was high in Chinese population. People younger than 60 years were the focus of prevention for cervical spondylosis. Moreover, the characters between male and female and among different age groups were different and required targeted interventions.

Eugenol, as an active compound isolated from Acorus gramineus, has been shown to protect against cerebral ischemia-reperfusion (I/R) injury. Nonetheless, the detailed neuroprotective mechanisms of eugenol in cerebral I/R injury have not been elaborated. In the present study, cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) in rats. HT22 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic cerebral I/R injury . The results showed that eugenol pre-treatment relieved cerebral I/R injury as evidenced by improving neurological deficits and reducing infarct volume. Autophagy was induced by MCAO, which was further promoted by eugenol administration. Moreover, rapamycin, an activator of autophagy, promoted eugenol-induced decreases in neurological score, infarct volume, brain water content, and apoptosis. However, pretreatment with 3-MA, an inhibitor of autophagy, led to the opposite results. Similarly, eugenol pretreatment increased the viability and restrained apoptosis of OGD/R-challenged HT22 cells. OGD/R-induced autophagy was strengthened by eugenol. Mechanically, eugenol promoted autophagy through regulating AMPK/mTOR/P70S6K signaling pathway and . In conclusion, pretreatment with eugenol attenuated cerebral I/R injury by inducing autophagy AMPK/mTOR/P70S6K signaling pathway.

Cronobacter sakazakii is a Gram-negative bacterium known for causing severe infections in neonates, particularly through contaminated infant formula. This study investigated the role of the outer membrane lipoprotein NlpD in the environmental tolerance of C. sakazakii . A nlpD knockout mutant was constructed, and its impact on desiccation resistance, biofilm formation, motility, and proteomic profiles was evaluated and compared with that of the wild-type strain. The nlpD mutant presented reduced desiccation tolerance, reduced ability to form a biofilm, and altered surface hydrophobicity and motility patterns. The complemented strain restored these phenotypic changes, confirming that the observed effects were specifically due to the deletion of nlpD . Proteomic analysis revealed significant differential expression of proteins involved in metabolic and biosynthetic pathways upon nlpD deletion. These findings emphasize the multifaceted role of NlpD in enhancing the environmental tolerance of C. sakazakii , suggesting its importance in the resilience and survival of the bacterium in adverse conditions.

Cancer cells, as well as surrounding stromal and inflammatory cells, form an inflammatory tumor microenvironment (TME) to promote all stages of carcinogenesis. As an emerging post-translational modification (PTM) of serine and threonine residues of proteins, O-linked-N-Acetylglucosaminylation (O-GlcNAcylation) regulates diverse cancer-relevant processes, such as signal transduction, transcription, cell division, metabolism and cytoskeletal regulation. Recent studies suggest that O-GlcNAcylation regulates the development, maturation and functions of immune cells. However, the role of protein O-GlcNAcylation in cancer-associated inflammation has been less explored. This review summarizes the current understanding of the influence of protein O-GlcNAcylation on cancer-associated inflammation and the mechanisms whereby O-GlcNAc-mediated inflammation regulates tumor progression. This will provide a theoretical basis for further development of anti-cancer therapies.

Background Brain metastases (BMs) are almost a norm and devastating complication of metastatic breast cancer (MBC), but patients with active BMs (untreated or progressing to prior local therapy) are usually excluded from participating in clinical trials. Trastuzumab deruxtecan (T-DXd) has shown remarkable intracranial activity in pretreated human epidermal growth factor receptor 2 (HER2)-positive MBC with active BMs in latest prospective trials, but real-world evidence about its efficacy and safety remains limited. Methods This real-world study enrolled patients with active BMs from HER2-positive/low MBC receiving at least one cycle T-DXd (5.4 mg/kg, Q3W) in three hospitals in China between June 2022 to May 2024. The primary endpoint was the best intracranial overall response rate (iORR) following the response assessment in neuro-oncology brain metastases criteria. Secondary endpoints included the intracranial and overall progression-free survival (iPFS-PFS), overall survival (OS), and safety. Results In total, 38 patients were enrolled, including 29 HER2-positive and 9 HER2-low MBC. Except for endocrine therapy, the median number of prior therapy lines was 2 (range 0–10). Among HER2-positive patients, one patient (11.1%) had a complete intracranial response and eighteen (62.1%) had a partial intracranial response as the best intracranial response, with an iORR of 65.5%. As for HER2-low patients, the iORR was 66.7%. During a median follow-up of 10.3 (range 1.53–24.4) months, the median iPFS and OS were not reached for both HER2-positive and HER2-low MBC, their 12-month iPFS rate stood at 79.8% (95% confidence interval (CI): 65.2–97.7%) and 51.9% (95% CI: 26.7–100.0%), respectively. In the HER2-positive cohort, the median PFS was 12.8 months (95% CI: 10.2-not reached) and the 12-month OS rate was 86.5% (95% CI: 69.4–100.0%). For HER2-low cohort, the median PFS and 12-month OS rate were 6.33 months (95% CI: 3.93-not reached) and 85.7% (95% CI: 63.3–100.0%), respectively. Most common adverse events were moderate and no new safety signals were observed. Conclusions In this real-world population, T-DXd yielded encouraging intracranial activity in HER2-positive/low MBC patients with active BMs with acceptable tolerance, which was aligned with previous clinical trials data. These results support the concept of T-DXd as systemic therapy for MBC patients with active BMs irrespective of HER2-positive/low.

Background Haemochromatosis is a genetic disease characterized by the excessive deposition of iron in various tissues and organs, eventually results in organ damage including cirrhosis, diabetes, cardiomyopathy, etc. SLC40A1 -related haemochromatosis is associated with gain-of-function mutations in the SLC40A1 gene, which encodes ferroportin. While sporadic reports of this condition exist in mainland China, the understanding of the phenotype and genetic pattern associated with the SLC40A1 p.Y333H mutation remains incomplete. Case presentation We report a pedigree with heterozygous p.Y333H mutation in Chinese Han population. The proband is a 64-year-old man complaining of persistent abnormality of liver enzyme levels for 1 year, with a history of knee joint pain, diabetes and skin pigmentation. He displayed markedly elevated serum ferritin level and transferrin saturation. Magnetic resonance imaging showed iron deposition in the liver, spleen, and pancreas, along with cirrhosis and splenomegaly. Whole exome sequencing identified a heterozygous allelic variant c.997T > C (p.Y333H). Genetic screening of family members identified four first-degree relatives and three second-degree relatives having the same mutation. Additional cases with this mutation from two published studies were included. Among the probands and screened relatives, all eight males aged over 30 y had ferritin level > 1000 µg/L, transferrin saturation > 90%. Four patients with organ damage in the present study received therapeutic phlebotomy, alleviating clinical symptoms and improving in transferrin saturation and serum ferritin. Conclusions This study reports the largest pedigree with heterozygous SLC40A1 p.Y333H mutation in the Chinese population to date. In Chinese families, males over 30 years old with hemochromatosis due to SLC40A1 p.Y333H mutation exhibit severe iron overload phenotypes.

BackgroundThere is a paucity of data regarding the prevalence of preoperative deep vein thrombosis (DVT) in patients with long bone (including femur, tibia and fibula) fractures of the lower limbs. We performed a meta-analysis to address the issue.MethodsElectronic databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, the VIP database, CNKI, and the Wanfang database, were systematic searched for original articles that reported the prevalence of preoperative DVT in long bone fractures of the lower limbs from January 2016 to September 2021. The prevalence of preoperative DVT was pooled using random-effects models, and subgroups were established according to study type, detection method, sample size and fracture site.ResultsTwenty-three articles reporting on 18,119 patients were eligible. The overall pooled preoperative DVT prevalence was 24.1% (95% CI 19.3–28.8%). In different subgroups, the preoperative DVT prevalences were 18.2–27.3%, 15.2–28.6%, 23.1–24.9%, 18.2–26.0% and 23.2–23.4% for different study designs, sample sizes, age groups, detection methods and fracture sites, respectively.ConclusionsDespite the heterogeneity among studies, this systematic review suggests that the prevalence of preoperative DVT, which may seriously affect the prognosis of patients, is high. Therefore, greater efforts should be devoted to the improvement of screening and prevention strategies for preoperative DVT in lower-extremity long bone fractures.Level of Evidence: Level III.Trial Registration The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42022324706.

Background Polycystic ovary syndrome (PCOS) is linked to non-alcoholic fatty liver disease (NAFLD). Biochemical, sex hormonal, and anthropometric indicators have been explored for screening NAFLD in PCOS patients. However, the accuracy of NAFLD screening using these indicators in PCOS patients remains uncertain. This study aimed to identify biochemical, sex hormonal, and anthropometric indicators associated with NAFLD in overweight and obese PCOS patients and assess the diagnostic efficacy of combined indicators. Methods This cross-sectional study (Clinical trial number ChiCTR1900020986; Registration date January 24th, 2019) involved 87 overweight or obese women with PCOS (mean age 29 ± 4 years). Measurements included anthropometric indices, biochemistry, sex hormone levels, and liver proton density fat fraction (PDFF). Correlation analysis, intergroup comparisons, and logistic regression analysis were used to identify risk factors for NAFLD (PDFF > 5.1%). The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value were used to determine cut-off values and evaluate diagnostic accuracy. Results Liver PDFF was 7.69% (3.93%, 14.80%) in overweight and obese PCOS patients, with 67.8% diagnosed with NAFLD. NAFLD was associated with increased body mass index (BMI), abdominal circumference (AC), and triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), glucose, insulin, and free testosterone (FT) levels, and with decreased high-density lipoprotein-cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels ( P  < 0.05). Risk factors for NAFLD in PCOS included BMI > 26.8 kg/m 2 , AC > 88.3 cm, triglyceride > 1.57 mmol/L, TC > 4.67 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, FT > 7.6 pg/mL and SHBG < 25 nmol/L ( β  = 1.411–2.667, P  < 0.005). A multi-indicator model including triglycerides, LDL-C, glucose, insulin, and SHBG showed higher diagnostic accuracy (AUC = 0.899, P  < 0.001) for screening NAFLD in PCOS patients than single indicators (AUC = 0.667–0.761, P  < 0.05). Conclusions Overweight and obese PCOS patients have higher incidences of liver PDFF and NAFLD. A multi-indicator model including triglycerides > 1.57 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, and SHBG < 25 nmol/L is highly accurate for screening NAFLD in overweight and obese PCOS patients.

New ambuic acid derivatives, pestallic acids R–V ( 1 − 5 ), together with ambuic acid ( 6 ), were isolated from the endophytic fungus Pestalotiopsis trachicarpicola SC-J551 derived from the fern Blechnum orientale L., of which compound 2 , being racemic, was separated to two optically pure enantiomers (+)- 2 and (−)- 2 . The structures including absolute configurations of these new compounds were elucidated by extensive spectroscopic analysis and theoretical simulations of their ECD spectra and 13 C NMR chemical shifts. Compounds 1 and 3 exhibited cytotoxicity against human carcinoma A549, HeLa, HepG2, and MCF-7 cells (IC 50 : 3.6–12.5 μM) and compound 3 was also active against Staphylococcus aureus and MRSA (MIC = 20 μg ml −1 ). Compound (±)- 2 showed inhibitory activity against LPS-induced NO release (IC 50  = 21.1 μM) and t -BHP-induced ROS production (IC 50  = 8.5 μM) in RAW264.7 macrophages.

Exosomes are extracellular vesicles (EVs) of ~20-200 nm diameter that shuttle DNAs, RNAs, proteins and other biomolecules between cells. The large number of biomolecules present in exosomes demands the frequent use of high-throughput analysis. This, in turn, requires technical replicates (TRs), and biological replicates (BRs) to produce accurate results. As the number and abundance of identified biomolecules varies between replicates (Rs), establishing the replicate variability predicted for the event under study is essential in determining the number of Rs required. Although there have been few reports of replicate variability in high throughput biological data, none of them focused on exosomes. Herein, we determined the replicate variability in protein profiles found in exosomes released from 3 lung adenocarcinoma cell lines, H1993, A549 and H1975. Since exosome isolates are invariably contaminated by a small percentage of ~200-300 nm microvesicles, we refer to our samples as exosome-enriched EVs (EE-EVs). We generated BRs of EE-EVs from each cell line, and divided each group into 3 TRs. All Rs were analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) and customized bioinformatics and biostatistical workflows (raw data available via ProteomeXchange: PXD012798). We found that the variability among TRs as well as BRs, was largely qualitative (protein present or absent) and higher among BRs. By contrast, the quantitative (protein abundance) variability was low, save for the H1975 cell line where the quantitative variability was significant. Importantly, our replicate strategy identified 90% of the most abundant proteins, thereby establishing the utility of our approach.