High-strength double-network silk fibroin based hydrogel loaded with Icariin and BMSCs to inhibit osteoclasts and promote osteogenic differentiation to enhance bone repair.

Large bone defects cause significant clinical challenges due to the lack of optimal grafts for effective regeneration. The tissue engineering way that requires the combination of biomaterials scaffold, stem cells and proper bioactive factors is a prospective method for large bone repair. Here, we synthesized a three-arm host-guest supramolecule (HGSM) to covalently crosslinking with the naturally derived polymer methacrylated silk fibroin (SFMA). The combination of HGSM and SFMA can form a high strength double-crosslinked hydrogel HGSFMA, that serve as the hydrogel scaffold for bone marrow mesenchymal stem cells (BMSCs) growing. Icariin (ICA) loaded in the HGSFMA hydrogel can promote the osteogenesis efficiency of BMSCs and inhibit the osteoclasts differentiation. Our findings demonstrated that the HGSFMA/ICA hydrogel effectively promoted the in vitro adhesion, proliferation, and osteogenic differentiation of BMSCs. Rat femoral defects model show that this hydrogel can completely repair femoral damage within 4 weeks and significantly promote the secretion of osteogenesis-related proteins. In summary, we have prepared an effective biomimetic bone carrier, offering a novel strategy for bone regeneration and the treatment of large-scale bone defects.

Errate: Enhanced Patient Comfort and Satisfaction with Early Oral Feeding after Thoracoscopic Lung Cancer Resection.

The published grant number was "OFJH2021008", while the correct should read "DFJH2021008". Reference: Yinghong Wu, Huiling Liu, Minghao Zhong, Xiyi Chen, Zhiqiong Ba, Guibin Qiao, Jiejie Feng, Xiuqun Zeng: Enhanced Patient Comfort and Satisfaction with Early Oral Feeding after Thoracoscopic Lung Cancer Resection. Med Sci Monit, 2023; 29: e941577. DOI: 10.12659/MSM.941577.

Machine learning for differentiating lung squamous cell cancer from adenocarcinoma using Clinical-Metabolic characteristics and 18F-FDG PET/CT radiomics.

Noninvasive differentiation between the squamous cell carcinoma (SCC) and adenocarcinoma (ADC) subtypes of non-small cell lung cancer (NSCLC) could benefit patients who are unsuitable for invasive diagnostic procedures. Therefore, this study evaluates the predictive performance of a PET/CT-based radiomics model. It aims to distinguish between the histological subtypes of lung adenocarcinoma and squamous cell carcinoma, employing four different machine learning techniques. A total of 255 Non-Small Cell Lung Cancer (NSCLC) patients were retrospectively analyzed and randomly divided into the training (n = 177) and validation (n = 78) sets, respectively. Radiomics features were extracted, and the Least Absolute Shrinkage and Selection Operator (LASSO) method was employed for feature selection. Subsequently, models were constructed using four distinct machine learning techniques, with the top-performing algorithm determined by evaluating metrics such as accuracy, sensitivity, specificity, and the area under the curve (AUC). The efficacy of the various models was appraised and compared using the DeLong test. A nomogram was developed based on the model with the best predictive efficiency and clinical utility, and it was validated using calibration curves. Results indicated that the logistic regression classifier had better predictive power in the validation cohort of the radiomic model. The combined model (AUC 0.870) exhibited superior predictive power compared to the clinical model (AUC 0.848) and the radiomics model (AUC 0.774). In this study, we discovered that the combined model, refined by the logistic regression classifier, exhibited the most effective performance in classifying the histological subtypes of NSCLC.

Cascade Dual Sites Modulate Local CO Coverage and Hydrogen-Binding Strength to Boost CO2 Electroreduction to Ethylene.

Rationally modulating the binding strength of reaction intermediates on surface sites of copper-based catalysts could facilitate C-C coupling to generate multicarbon products in an electrochemical CO2 reduction reaction. Herein, theoretical calculations reveal that cascade Ag-Cu dual sites could synergistically increase local CO coverage and lower the kinetic barrier for CO protonation, leading to enhanced asymmetric C-C coupling to generate C2H4. As a proof of concept, the Cu3N-Ag nanocubes (NCs) with Ag located in partial Cu sites and a Cu3N unit center are successfully synthesized. The Faraday efficiency and partial current density of C2H4 over Cu3N-Ag NCs are 7.8 and 9.0 times those of Cu3N NCs, respectively. In situ spectroscopies combined with theoretical calculations confirm that Ag sites produce CO and Cu sites promote asymmetric C-C coupling to *COCHO, significantly enhancing the generation of C2H4. Our work provides new insights into the cascade catalysis strategy at the atomic scale for boosting CO2 to multicarbon products.

ARRB1 downregulates acetaminophen-induced hepatoxicity through binding to p-eIF2α to inhibit ER stress signaling.

Acetaminophen (APAP) stands as the predominant contributor to drug-induced liver injury (DILI), and limited options are available. ß-Arrestin1 (ARRB1) is involved in numerous liver diseases. However, the role of ARRB1 in APAP-induced liver injury remained uncertain. Wild-type (WT) and ARRB1 knockout (KO) mice were injected with APAP and sacrificed at the indicated times. The histological changes, inflammation, endoplasmic reticulum (ER) stress, and apoptosis were then evaluated. Hepatic cell lines AML-12 and primary hepatocytes were used for in vitro analyses. Systemic ARRB1-KO mice were susceptible to APAP-induced hepatotoxicity, as indicated by larger areas of centrilobular necrosis area and higher levels of ALT, AST, and inflammation level. Moreover, ARRB1-KO mice exhibited increased ER stress (indicated by phosphorylated α subunit of eukaryotic initiation factor 2 (p-eIF2α)-activating transcription factor 4 (ATF4)-CCAAT-enhancer-binding protein homologous protein (CHOP)) and apoptosis (indicated by cleaved caspase 3). Further rescue experiments demonstrated that the induction of apoptosis was partially mediated by ER stress. Overexpression of ARRB1 alleviated APAP-induced ER stress and apoptosis. Moreover, co-IP analysis revealed that ARRB1 directly bound to p-eIF2α and eIF2α. ARRB1 protected against APAP-induced hepatoxicity through targeting ER stress and apoptosis. ARRB1 is a prospective target for treating APAP-induced DILI.

Activated hepatic stellate cell-derived Bmp-1 induces liver fibrosis via mediating hepatocyte epithelial-mesenchymal transition.

Liver fibrosis is a reparative response to injury that arises from various etiologies, characterized by activation of hepatic stellate cells (HSCs). Periostin, a secreted matricellular protein, has been reported to participate in tissue development and regeneration. However, its involvement in liver fibrosis remains unknown. This study investigated the roles and mechanisms of Periostin in phenotypic transition of HSCs and relevant abnormal cellular crosstalk during liver fibrosis. The fate of hepatic stellate cells (HSCs) during liver fibrogenesis was investigated using single-cell and bulk RNA sequencing profiles, which revealed a significant proliferation of activated HSCs (aHSCs) in fibrotic livers of both humans and mice. αSMA-TK mice were used to demonstrate that depletion of proliferative aHSCs attenuates liver fibrosis induced by carbon tetrachloride and 3,5-diethoxycarbonyl-1,4-dihydrocollidine. Through integrating data from single-cell and bulk sequencing, Periostin was identified as a distinctive hallmark of proliferative aHSC subpopulation. Elevated levels of Periostin were detected in fibrotic livers of both humans and mice, primarily within aHSCs. However, hepatic Periostin levels were decreased along with depletion of proliferative aHSCs. Deficiency of Periostin led to reduced liver fibrosis and suppressed hepatocyte epithelial-mesenchymal transition (EMT). Periostin-overexpressing HSCs, exhibiting a proliferative aHSC phenotype, release bone morphogenetic protein-1 (Bmp-1), which activates EGFR signaling, inducing hepatocyte EMT and contributing to liver fibrosis. In conclusion, Periostin in aHSCs drives their acquisition of a proliferative phenotype and the release of Bmp-1. Proliferative aHSC subpopulation-derived Bmp-1 induces hepatocyte EMT via EGFR signaling, promoting liver fibrogenesis. Bmp-1 and Periostin should be potential therapeutic targets for liver fibrosis.

Development and validation of a 18F-FDG PET/CT radiomics nomogram for predicting progression free survival in locally advanced cervical cancer: a retrospective multicenter study.

BACKGROUND: The existing staging system cannot meet the needs of accurate survival prediction. Accurate survival prediction for locally advanced cervical cancer (LACC) patients who have undergone concurrent radiochemotherapy (CCRT) can improve their treatment management. Thus, this present study aimed to develop and validate radiomics models based on pretreatment 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) images to accurately predict the prognosis in patients. METHODS: The data from 190 consecutive patients with LACC who underwent pretreatment 18F-FDG PET-CT and CCRT at two cancer hospitals were retrospectively analyzed; 176 patients from the same hospital were randomly divided into training (n = 117) and internal validation (n = 50) cohorts. Clinical features were selected from the training cohort using univariate and multivariate Cox proportional hazards models; radiomic features were extracted from PET and CT images and filtered using least absolute shrinkage and selection operator and Cox proportional hazard regression. Three prediction models and a nomogram were then constructed using the previously selected clinical, CT and PET radiomics features. The external validation cohort that was used to validate the models included 23 patients with LACC from another cancer hospital. The predictive performance of the constructed models was evaluated using receiver operator characteristic curves, Kaplan Meier curves, and a nomogram. RESULTS: In total, one clinical, one PET radiomics, and three CT radiomics features were significantly associated with progression-free survival in the training cohort. Across all three cohorts, the combined model displayed better efficacy and clinical utility than any of these parameters alone in predicting 3-year progression-free survival (area under curve: 0.661, 0.718, and 0.775; C-index: 0.698, 0.724, and 0.705, respectively) and 5-year progression-free survival (area under curve: 0.661, 0.711, and 0.767; C-index, 0.698, 0.722, and 0.676, respectively). On subsequent construction of a nomogram, the calibration curve demonstrated good agreement between actually observed and nomogram-predicted values. CONCLUSIONS: In this study, a clinico-radiomics prediction model was developed and successfully validated using an independent external validation cohort. The nomogram incorporating radiomics and clinical features could be a useful clinical tool for the early and accurate assessment of long-term prognosis in patients with LACC patients who undergo concurrent chemoradiotherapy.

Synthetic Biology-based Construction of Unnatural Perylenequinones with Improved Photodynamic Anticancer Activities.

The construction of structural complexity and diversity of natural products is crucial for drug discovery and development. To overcome high dark toxicity and poor photostability of natural photosensitizer perylenequinones (PQs) for photodynamic therapy, herein, we aim to introduce the structural complexity and diversity to biosynthesize the desired unnatural PQs in fungus Cercospora through synthetic biology-based strategy. Thus, we first elucidate the intricate biosynthetic pathways of class B PQs and reveal how the branching enzymes create their structural complexity and diversity from a common ancestor. This enables the rational reprogramming of cercosporin biosynthetic pathway in Cercospora to generate diverse unnatural PQs without chemical modification. Among them, unnatural cercosporin A displays remarkably low dark toxicity and high photostability with retention of great photodynamic anticancer and antimicrobial activities. Moreover, it is found that, unlike cercosporin, unnatural cercosporin A could be selectively accumulated in cancer cells, providing potential targets for drug development. Therefore, this work provides a comprehensive foundation for preparing unnatural products with customized functions through synthetic biology-based strategies, thus facilitating drug discovery pipelines from nature.

Enhanced Patient Comfort and Satisfaction with Early Oral Feeding after Thoracoscopic Lung Cancer Resection.

BACKGROUND The study aimed to compare the patient-reported outcomes in patients who underwent early vs conventional feeding after thoracoscopic lung cancer resection. MATERIAL AND METHODS The study enrolled 211 patients who underwent thoracoscopic lung cancer resection at a tertiary hospital between July 2021 and July 2022. Patients were randomly assigned to the conventional group or the early feeding group. There were 106 patients in the early feeding group and 105 patients in the conventional group. The conventional group received water 4 h after extubation and liquid/semi-liquid food 6 h after extubation. In contrast, the early feeding group received water 1 h after extubation and liquid/semi-liquid food 2 h after extubation. The primary outcomes were the degree of hunger, thirst, nausea, and vomiting. The secondary outcomes were postoperative complications, duration of hospital stay, and chest tube drainage. RESULTS No differences were found between the 2 groups in the degrees of postoperative nausea, vomiting, or pain after extubation for 1, 2, 4, and 8 h. Postoperative complications, duration of chest tube drainage, and duration of hospital stay were also similar (P=0.567, P=0.783, P=0.696). However, the hunger and thirst scores after extubation for 2 h and 4 h decreased and were lower in the early feeding group (both P<0.001). No patients developed choking, postoperative aspiration, gastrointestinal obstruction, or other complications. CONCLUSIONS Early oral feeding after thoracoscopic lung cancer resection is safe and can increase patient comfort postoperatively.

scHiCDiff: detecting differential chromatin interactions in single-cell Hi-C data.

SUMMARY: Here, we presented the scHiCDiff software tool that provides both nonparametric tests and parametirc models to detect differential chromatin interactions (DCIs) from single-cell Hi-C data. We thoroughly evaluated the scHiCDiff methods on both simulated and real data. Our results demonstrated that scHiCDiff, especially the zero-inflated negative binomial model option, can effectively detect reliable and consistent single-cell DCIs between two conditions, thereby facilitating the study of cell type-specific variations of chromatin structures at the single-cell level. AVAILABILITY AND IMPLEMENTATION: scHiCDiff is implemented in R and freely available at GitHub (https://github.com/wmalab/scHiCDiff).

Impact of the intensive psychological intervention care on post-traumatic stress disorder and negative emotions of teenage female patients seeking an induced abortion.

Aim: This study aimed to investigate the effects of intensive psychological intervention care on adverse emotions and post-traumatic stress disorder (PTSD) symptoms in female teenage patients after induced abortion. Methods: This prospective cohort study included 100 teenage female patients seeking induced abortion who were randomly divided into two groups: the intervention group (n = 50) and the control group (n = 50). The intervention group received intensive psychological intervention care, while the control group received standard routine nursing. The scores of the PTSD checklist for DSM-5 (PCL-5), self-rating depression (SDS), and self-rating anxiety scale (SAS) were compared between the two groups at 1 month and 3 months after the operation. Results: The intervention group had lower risk of developing PTSD (24% vs. 44%), depression (10% vs. 32%), and anxiety (0% vs. 12%) symptoms at 1 month after the surgery. However, there were no significant differences observed between the two groups at 3 months after the surgery. Furthermore, the intervention group had significantly lower scores in PCL-5 (27.4 ± 5.4 vs. 31.8 ± 5.7; 20.5 ± 7.1 vs. 25.0 ± 7.5; p < 0.05), SDS (31.8 ± 5.4 vs. 37.8 ± 6.6; 26.8 ± 5.0 vs. 31.4 ± 7.2; p < 0.05), and SAS (32.7 ± 5.0 vs. 39.8 ± 6.9; 25.0 ± 2.7 vs. 27.5 ± 2.8; p < 0.05) at 1 month and 3 months after induced abortion. Conclusion: These findings suggest that intensive psychological intervention care can reduce the incidence and severity of depression, anxiety, and PTSD symptoms in teenage patients who undergo induced abortion. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=185200, identifier ChiCTR2300067531.

Automatic Detection of Brain Metastases in T1-Weighted Construct-Enhanced MRI Using Deep Learning Model.

As a complication of malignant tumors, brain metastasis (BM) seriously threatens patients' survival and quality of life. Accurate detection of BM before determining radiation therapy plans is a paramount task. Due to the small size and heterogeneous number of BMs, their manual diagnosis faces enormous challenges. Thus, MRI-based artificial intelligence-assisted BM diagnosis is significant. Most of the existing deep learning (DL) methods for automatic BM detection try to ensure a good trade-off between precision and recall. However, due to the objective factors of the models, higher recall is often accompanied by higher number of false positive results. In real clinical auxiliary diagnosis, radiation oncologists are required to spend much effort to review these false positive results. In order to reduce false positive results while retaining high accuracy, a modified YOLOv5 algorithm is proposed in this paper. First, in order to focus on the important channels of the feature map, we add a convolutional block attention model to the neck structure. Furthermore, an additional prediction head is introduced for detecting small-size BMs. Finally, to distinguish between cerebral vessels and small-size BMs, a Swin transformer block is embedded into the smallest prediction head. With the introduction of the F2-score index to determine the most appropriate confidence threshold, the proposed method achieves a precision of 0.612 and recall of 0.904. Compared with existing methods, our proposed method shows superior performance with fewer false positive results. It is anticipated that the proposed method could reduce the workload of radiation oncologists in real clinical auxiliary diagnosis.

Study on injectable silver-incorporated calcium phosphate composite with enhanced antibacterial and biomechanical properties for fighting bone cement-associated infections.

Although commonly used in orthopedic surgery, bone cements often face a high risk of post-operative infection. Developing bone cement with antibacterial capability is an effective path for eliminating implant-associated infections. Herein, the potential of silver ions (Ag+) and silver nanoparticles (AgNPs) in modifying CPC for long-term antibacterial property was investigated. Ag+ ions or AgNPs of various concentrations were incorporated in starch-modified calcium phosphate bone cement (CPB) to obtain Ag+-containing (Ag+@CPB) and AgNPs-containing (AgNP@CPB) bone cements. The results showed that all silver-containing CPBs had setting times of about 25-40 min, compressive strengths of greater than 22 MPa, high cytocompatibility but inhibitory effect on Staphylococcus aureus growth. After soaking for 1 week, the mechanical properties and the cytocompatibility of all cements revealed no significant changes, but only CPB with a relatively high content of Ag+ (H-Ag+@CPB) maintained good antibacterial capability over the tested time period. In addition, all the cements showed high injectability and interdigitating capability in cancellous bone and demonstrated augmentation effect on the cannulated pedicle screws fixation in the Sawbones model. In summary, the sustainable antibacterial capability and enhanced biomechanical properties demonstrated that Ag+ ions were more suitable for the fabrication of antibacterial CPC compared to AgNPs. Also, the H-Ag+@CPB, with good injectability, high cytocompatibility, good interdigitating and biomechanical property in cancellous bone, and sustainable antibacterial effects, bears great potential for the treatments of bone infections or implant-associated infections.

Diagnostic accuracy of the Copenhagen Index in ovarian malignancy: A meta-analysis.

OBJECTIVE: To assess the diagnostic value of the Copenhagen index for ovarian malignancy. METHODS: PubMed, Web of Science, the Cochrane Library, Embase, CBM, CNKI, and WanFang databases were searched throughout June 2021. Statistical analyses were performed using Stata 12, Meta-DiSc, and RevMan 5.3. The pooled sensitivity, specificity, and diagnostic odds ratio were calculated, the summary receiver operating characteristic curve was drawn, and the area under the curve was calculated. RESULTS: Ten articles, including 11 studies with a total of 5266 patients, were included. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.82 [95% CI (0.80-0.83)], 0.88 [95% CI (0.87-0.89)], and 57.31 [95% CI (32.84-100.02)], respectively. The area under the summary receiver operating characteristics curve and the Q index were 0.9545 and 0.8966, respectively. CONCLUSION: Our systematic review shows that the sensitivity and specificity of the Copenhagen index are high enough for it to be used in a clinical setting to provide accurate ovarian cancer diagnosis without considering menopausal status.

PTTG1 Reprograms Asparagine Metabolism to Promote Hepatocellular Carcinoma Progression.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a poor prognosis. Pituitary tumor transforming gene 1 (PTTG1) is highly expressed in HCC, suggesting it could play an important role in hepatocellular carcinogenesis. Here, we evaluated the impact of PTTG1 deficiency on HCC development using a diethylnitrosamine (DEN)-induced HCC mouse model and a hepatitis B virus (HBV) regulatory X protein (HBx)-induced spontaneous HCC mouse model. PTTG1 deficiency significantly suppressed DEN- and HBx-induced hepatocellular carcinogenesis. Mechanistically, PTTG1 promoted asparagine synthetase (ASNS) transcription by binding to its promoter, and asparagine (Asn) levels were correspondingly increased. The elevated levels of Asn subsequently activated the mTOR pathway to facilitate HCC progression. In addition, asparaginase treatment reversed the proliferation induced by PTTG1 overexpression. Furthermore, HBx promoted ASNS and Asn metabolism by upregulating PTTG1 expression. Overall, PTTG1 is involved in the reprogramming of Asn metabolism to promote HCC progression and may serve as a therapeutic and diagnostic target for HCC. SIGNIFICANCE: PTTG1 is upregulated in hepatocellular carcinoma and increases asparagine production to stimulate mTOR activity and promote tumor progression.

Associations of Colonoscopy and Risk of Hypoglycemia in Patients with Type 2 Diabetes.

Purpose: Inpatients undergoing colonoscopy may be at increased risk of hypoglycemia. However, few high-quality studies have examined the relationship between hypoglycemia and colonoscopy in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A total of 1016 patients from a large tertiary hospital were enrolled in this retrospective study. We collected demographic information, laboratory indices, colonoscopy information and hypoglycemia information from the enrolled patients during hospitalization. Logistic regression analysis was adopted to estimate the adjusted odds ratios to determine the association between hypoglycemia and colonoscopy. Results: Hypoglycemia occurred in 80 of 788 (10.1%) patients without colonoscopy exposure and 37 of 228 (16.2%) patients with colonoscopy exposure. 25 patients (67.6%) had hypoglycemic events from 3 hours to 68 hours after the end of colonoscopy. Adjusting for demographic and clinical covariates, the risk of hypoglycemia was 1.99 times higher in those who underwent colonoscopy than in those who did not (OR 1.99, 95% CI 1.25-3.19). The association was consistent in subgroups of females, the elderly, the overweight patients, patients with long duration of disease or patients with suboptimal glycemic control. Conclusion: A strong association between colonoscopy and an increased risk of hypoglycemia is observed in patients with T2DM. When performing a colonoscopy for diabetics, the risk of hypoglycemia should be considered even within 68 hours after colonoscopy.

Enhanced production of aspochalasin D through genetic engineering of Aspergillus flavipes.

Aspochalasin D (AD) belongs to the polyketide-amino acid hybrid natural products with anti-cancer, anti-bacterial, and anti-fouling bioactivities. However, the low production limits its further application. In this study, AD was separated and identified from Aspergillus flavipes 3.17641. Next, besides the optimization of culture conditions using a single-factor experiment and response surface methodology, metabolic engineering was employed to increase the AD production. It shows that the deletion of the shunt gene aspoA and overexpression of the pathway-specific regulator aspoG significantly improve the AD production. Its production reached to 812.1 mg/L under the optimized conditions, with 18.5-fold increase. Therefore, this study not only provides a general method for improving the production of similar natural products in other fungi, but also enables the further biological function development of AD in agriculture and pharmaceutical. KEY POINTS: • The Aspochalasin D (AD) production was improved by optimizing culture conditions. • The deletion of the shunt gene aspoA increased the AD production. • Overexpression of the pathway regulator aspoG further improved the AD production.

Novel resorbable bone wax containing ß-TCP and starch microspheres for accelerating bone hemostasis and promoting regeneration.

Traditional non-resorbable bone wax has been used in clinical surgery for more than 100 years. However, residual bone wax has been proven to cause numerous complications. In this study, a novel resorbable bone wax was designed to overcome the disadvantages of traditional non-resorbable bone wax. Alkylene oxide copolymers were used as the main component of resorbable bone wax; additionally, ß-tricalcium phosphate and starch microspheres were added to enhance bone regeneration and hemostatic ability. This novel resorbable bone wax has a high potential for clinical translation and is expected to be developed as a substitute for traditional bone wax.

PTTG1 alleviates acute alcoholic liver injury by inhibiting endoplasmic reticulum stress-induced hepatocyte pyroptosis.

BACKGROUND & AIMS: Heavy drinking is a primary cause of alcoholic liver injury (ALI). Pituitary tumour transforming gene 1 (PTTG1) is involved in the occurrence and development of hepatocellular carcinoma (HCC), which is a well-known inflammation-related cancer with various aetiologies, including alcohol consumption. However, the role of PTTG1 in alcohol-induced liver injury and inflammation is not clear. METHODS: Blood samples were collected from patients with acute alcohol intoxication (n = 20) and healthy controls (n = 20). PTTG1 knockout (KO) mice and PTTG1 transgenic (TG) mice were given a single gavage of alcohol (5 g/kg, 50%) to construct the alcohol-induced liver injury. RESULTS: We found that serum PTTG1 levels were downregulated in acute ALI patients. In addition, acute alcohol administration significantly reduced PTTG1 levels in the serum and liver of mice. Compared to wild-type mice, PTTG1 KO mice had more serious liver injury, which was accompanied by worsened hepatic endoplasmic reticulum (ER) stress and hepatocyte pyroptosis induced by alcohol. Similarly, PTTG1 deficiency exacerbated alcohol-induced cell death in primary mouse hepatocytes and LO2 cells, by increasing hepatic ER stress and pyroptosis. Importantly, TUDCA, an ER stress inhibitor, could blocked alcohol-induced hepatic pyroptosis in PTTG1 knockdown LO2 cells. Finally, overexpression of PTTG1 substantially attenuated alcohol-induced liver injury by reducing ER stress and hepatic pyroptosis in mice. CONCLUSIONS: We demonstrated that PTTG1 participates in ALI and has a protective effect against alcohol-induced hepatic ER stress and pyroptosis.

Prevalent characteristics of human papillomavirus infection in 29,508 women in Jinshan District, Shanghai.

OBJECTIVE: This study aimed to investigate the prevalence characteristics of human papillomavirus (HPV) infections in 29,508 female cases in Jinshan District, Shanghai. MATERIALS AND METHODS: The current research represents a retrospective study that included 29,508 women who received cervical screening in the Jinshan Branch of Shanghai Sixth People's Hospital from 2010 to 2020. The overall prevalence, distribution types, age-specific prevalence and annual trends were analysed. RESULTS: The overall HPV infection rate among the patients was 21.97%. They were primarily high-risk HPV (HR-HPV) infections (20.30%) and single HPV infections (15.91%). A general decline in HPV and HR-HPV prevalence was observed with time from 33.52% to 25.45% in 2011 to 21.47% and 20.18% in 2020. The most common HPV genotypes were HPV52, HPV16, HPV58, HPV51, HPV53 and HPV68. The infection rates of HPV genotypes, including HPV6, HPV11, HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV42, HPV43, HPV66 and HPV68, showed overall declines across different years. The age-specific prevalence of total HPV and HR-HPV infections formed an approximate U-shaped curve with two peaks, one in the ≥55 age group (29.75%, 28.43%) and the other in the <25 age group (22.93%, 20.85%). Both total HPV and HR-HPV infection rates decreased to their lowest in the 25-34-year age groups. CONCLUSIONS: The prevalence of HPV infections showed a downward tendency with time. Single HPV genotype infections and HR-HPV infections were predominantly detected. The after prevalent characteristics of HPV can help to guide HPV vaccinations and cervical cancer screenings: 1) non-HPV16/HPV18 H R-HPV genotypes were prevalent; 2) non-vaccine-covered HPV53, HPV51 and HPV68 were also prevalent; 3) women above the age of 55 years had the highest HPV and HR-HPV infection rates.