Presepsin as a prognostic biomarker in COVID-19 patients: combining clinical scoring systems and laboratory inflammatory markers for outcome prediction.

BACKGROUND: There is still limited research on the prognostic value of Presepsin as a biomarker for predicting the outcome of COVID-19 patients. Additionally, research on the combined predictive value of Presepsin with clinical scoring systems and inflammation markers for disease prognosis is lacking. METHODS: A total of 226 COVID-19 patients admitted to Beijing Youan Hospital's emergency department from May to November 2022 were screened. Demographic information, laboratory measurements, and blood samples for Presepsin levels were collected upon admission. The predictive value of Presepsin, clinical scoring systems, and inflammation markers for 28-day mortality was analyzed. RESULTS: A total of 190 patients were analyzed, 83 (43.7%) were mild, 61 (32.1%) were moderate, and 46 (24.2%) were severe/critically ill. 23 (12.1%) patients died within 28 days. The Presepsin levels in severe/critical patients were significantly higher compared to moderate and mild patients (p < 0.001). Presepsin showed significant predictive value for 28-day mortality in COVID-19 patients, with an area under the ROC curve of 0.828 (95% CI: 0.737-0.920). Clinical scoring systems and inflammation markers also played a significant role in predicting 28-day outcomes. After Cox regression adjustment, Presepsin, qSOFA, NEWS2, PSI, CURB-65, CRP, NLR, CAR, and LCR were identified as independent predictors of 28-day mortality in COVID-19 patients (all p-values < 0.05). Combining Presepsin with clinical scoring systems and inflammation markers further enhanced the predictive value for patient prognosis. CONCLUSION: Presepsin is a favorable indicator for the prognosis of COVID-19 patients, and its combination with clinical scoring systems and inflammation markers improved prognostic assessment.

Three-Dimensional-Scanning of Pipe Inner Walls Based on Line Laser.

In this study, an innovative laser 3D-scanning technology is proposed to scan pipe inner walls in order to solve the problems of the exorbitant expenses and operational complexities of the current equipment for the 3D data acquisition of the pipe inner wall, and the difficulty of both the efficiency and accuracy of traditional light stripe-center extraction methods. The core of this technology is the monocular-structured light 3D scanner, the image processing strategy based on tracking speckles, and the improved gray barycenter method. The experimental results demonstrate a 52% reduction in the average standard error of the improved gray barycenter method when compared to the traditional gray barycenter method, along with an 83% decrease in the operation time when compared to the Steger method. In addition, the size data of the inner wall of the pipe obtained using this technology is accurate, and the average deviation of the inner diameter and length of the pipe is less than 0.13 mm and 0.41 mm, respectively. In general, it not only reduces the cost, but also ensures high efficiency and high precision, providing a new and efficient method for the 3D data acquisition of the inner wall of the pipe.

Two microRNAs of plasma-derived small extracellular vesicles as biomarkers for metastatic non-small cell lung cancer.

BACKGROUND: MicroRNAs (miRNAs) of plasma-derived small extracellular vesicles (sEVs) have been proven to be associated with metastasis in several types of cancer. This study aimed to detect miRNAs of plasma-derived sEVs as potential biomarkers for metastatic non-small cell lung cancer (NSCLC). METHODS: We assessed the miRNA profiles of plasma-derived sEVs from healthy individuals as the control group (CT group), NSCLC patients without distant organ metastasis as the NM-NSCLC group and patients with distant organ metastasis as the M-NSCLC group. Next-generation sequencing (NGS) was performed on samples, and differentially expressed miRNAs (DEMs) of the three groups were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) and ClueGO were used to predict potential pathways of DEMs. MiRNA enrichment analysis and annotation tool (miEAA) was used to understand changes in the tumour microenvironment in NSCLC. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) analysis was used to validate target miRNAs. RESULT: NGS was performed on 38 samples of miRNAs of plasma-derived sEVs, and DEMs were screened out between the above three groups. Regarding the distribution of DEMs in the NM-NSCLC and M-NSCLC groups, KEGG pathway analysis showed enrichment in focal adhesion and gap junctions and ClueGO in the Rap1 and Hippo signaling pathways; miEAA found that fibroblasts were over-represented. From our screening, miRNA-200c-3p and miRNA-4429 were found to be predictive DEMs among the CT, NM-NSCLC and M-NSCLC groups, and qRT‒PCR was applied to verify the results. Finally, it was revealed that expression levels of miR-200c-3p and miR-4429 were significantly upregulated in M-NSCLC patients. CONCLUSION: This study identified miRNA-200c-3p and miRNA-4429 as potential biomarkers for NSCLC metastasis.

Relationship between geriatric nutritional risk index and osteoporosis in type 2 diabetes in Northern China.

BACKGROUND: Osteoporosis is a very common bone disease in the elderly population and can lead to fractures and disability. Malnutrition can lead to osteoporosis. The geriatric nutritional risk index (GNRI) is a tool used to assess the risk of malnutrition and complications associated with nutritional status in older patients and is a crucial predictor of many diseases. Hence, this study investigated the association between the GNRI and the presence of osteoporosis and assessed the value of this index for predicting osteoporosis in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study enrolled 610 elderly patients with T2DM. General and laboratory data of the patients were collected, along with their measurements of bone mineral density (BMD). The GNRI was calculated based on ideal body weight and serum albumin (ABL) levels. Correlation analysis was performed to determine the relationship between the GNRI and BMD and bone metabolism indices. The GNRI predictive value for osteoporosis development was analyzed through logistic regression analysis and by creating a receiver operating characteristic curve (ROC), calculating the area under the curve (AUC). RESULTS: All patients were divided into the no-nutritional risk and nutritional risk groups. Compared with the no-nutritional risk group, the nutritional risk group had a longer diabetes course, older age, higher HbA1c levels, higher prevalence of osteoporosis; lower BMI, ABL,triglyceride (TG),Calcium (Ca),25-hydroxy-vitamin-D(25(OH)D),and parathyroid hormone(PTH) and lower femoral neck BMD,total hip BMD (P < 0.05). All patients were also assigned to the non-osteoporosis and osteoporosis groups. The non-osteoporosis group had higher GNRI values than the osteoporosis group (P < 0.05). Correlation analysis revealed a positive correlation between the GNRI and lumbar BMD, femoral neck BMD, and total hip BMD (P < 0.05). After the adjustment for confounding factors, Spearman's correlation analysis revealed that the GNRI was positively correlated with Ca, 25(OH)D, and PTH and negatively correlated with alkaline phosphatase (ALP) and procollagen of type-1 N-propeptide (P1NP). Regression analysis exhibited that the GNRI was significantly associated with osteoporosis. The ROC curve analysis was performed using the GNRI as the test variable and the presence of osteoporosis as the status variable. This analysis yielded an AUC for the GNRI of 0.695 and was statistically significant (P < 0.05). CONCLUSIONS: A lower GNRI among T2DM patients in northern China is associated with a higher prevalence of osteoporosis.

Influence of VEGFR2 gene polymorphism on the clinical outcomes of apatinib for patients with chemotherapy-refractory extensive-stage SCLC: a real-world retrospective study.

PURPOSE: Great individual differences were observed regarding the efficacy of apatinib clinically. The aim of present study was to investigate the influence of vascular endothelial growth factor receptor2 (VEGFR2) gene polymorphism on the clinical outcomes of apatinib for patients with chemotherapy-refractory extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 128 patients with chemotherapy-refractory ES-SCLC who were treated with apatinib at an initial dosage of 250 or 500 mg were included in this study. The change of target lesions was assessed. Overall response rate (ORR) was evaluated. Prognosis was carried out and safety profile was documented. Additionally, peripheral blood and biopsy cancer tissue specimens of the patients with SCLC were collected for the analysis of polymorphism and VEGFR2 gene mRNA expression, respectively. The association between genotype status and baseline characteristics was performed. Univariate analysis of genotype status and prognosis was carried out using Kaplan-Meier survival analysis and multivariate analysis were adjusted by Cox regression analysis. RESULTS: Efficacy of apatinib included partial response (PR) in 15 patients, stable disease (SD) in 86 patients, progressive disease (PD) in 27 patients. Therefore, ORR of the 128 patients with ES-SCLC was 11.7%, and disease control rate (DCR) was 78.9%. Prognosis suggested that the median progression-free survival (PFS) and overall survival (OS) of the 128 patients with ES-SCLC was 4.2 months and 8.2 months, respectively. The polymorphism analysis focusing on VEGFR2 gene indicated that one single nucleotide polymorphism 889C>T was of clinical significance. Prevalence of 889C>T among the 128 patients with SCLC were as follows: CC genotype 87 cases (68.0%), CT genotype 38 cases (29.7%) and TT genotype 3 cases (2.3%), the minor allele frequency of 889C>T was 0.17, which was in accordance with Hardy-Weinberg Equilibrium (P = 0.628). Patients with CT and TT genotypes were merged in the subsequent analysis. Prognosis analysis exhibited that the median PFS of patients with CT/TT genotype and CC genotype was 3.3 and 5.0 months, respectively (P = 0.02). Furthermore, the median OS of patients was 5.5 and 9.0 months, respectively (P = 0.008). Additionally, multivariate Cox regression analysis of OS demonstrated that CT/TT genotype was an independent factor for OS [Hazard ratio (HR) = 0.64, P = 0.019]. However, the safety profile according to genotype status of 889C>T failed to show significant difference. Interestingly, mRNA expression analysis suggested that the mRNA expression of VEGFR2 in cancer tissues were significantly different according to CC and CT/TT genotypes (P < 0.001). CONCLUSION: The administration with apatinib for patients with chemotherapy-refractory ES-SCLC was of potential clinical significance. The clinical outcomes of patients with ES-SCLC who were treated with apatinib could be impacted by VEGFR2 889C>T polymorphism through mediating the VEGFR2 mRNA expression.

Preparation of the lingual canal in mandibular first premolar with canal bifurcation.

The aim of this study was to establish an effective method of locating and negotiating the lingual canal in mandibular first premolars with two canals during root canal preparation. A total of 125 mandibular first premolars with radicular grooves were collected, and after micro-computed tomography scanning, 50 mandibular first premolars with a Vertucci V/III canal form were selected based on the inclusion criteria. Access cavities were prepared, and the lingual canals (LCs) were searched in four following steps: step 1 direct vision and a straight K-file; step 2 stereomicroscopy and a straight K-file; step 3 stereomicroscopy and a pre-curved K-file; and step 4 a long-neck bur. After localization, the LCs were instrumented. In most cases, access to the LC was achieved by step 2 (19/50, 38%) or step 3 (22/50, 44%). In three cases (6%), step 1 alone was enough to achieve access to the orifice, and in six cases (12%), access to the lingual canal was not achieved until step 4. Overall, 43 of the 50 mandibular first premolars (86%) were successfully instrumented, and the remaining seven failed. Two cases failed in the process of negotiating the canal to full length and five cases failed due to procedural errors (ledge formation, canal perforation, vertical fracture, or instrument separation). The LC in mandibular first premolars is a major endodontic challenge. A stereomicroscope and a pre-curved K file are suggested to be valuable tools for detecting and accessing the extra LC.

Investigation on the adsorption of antibiotics from water by metal loaded sewage sludge biochar.

Application of sewage sludge biochar as an adsorbent for antibiotics treatment has obtained special attention owning to its low cost and surface functionality. Three metal ions were selected to modify sewage sludge biochar through the pyrolysis with the metal loaded method. Fe loaded sewage sludge biochar (BC-Fe), Al loaded sewage sludge biochar (BC-Al) and Mn loaded sewage sludge biochar (BC-Mn) were characterized and used to explore the performance of adsorbing tetracycline (TC), sulfamethoxazole (SMZ) and amoxicillin (AMC). BC-Fe, BC-Al and BC-Mn possessed rougher surfaces, larger specific surface area and better pore structure. Intra-particle diffusion and Langmuir models were more suitable to describe the adsorption process. The maximum adsorption amount of TC, SMZ and AMC could reach 123.35, 99.01 and 109.89 mg/g by BC-Fe. Furthermore, the main mechanism of antibiotics adsorption by metal loaded sewage sludge biochars might be pores filling, Van der Waals forces and H-bonding. The study can not only solve the problems associated with the pollution of antibiotics from wastewater, but also reduced the treatment pressure of sewage sludge effectively.

Durability of Interferon-induced Hepatitis B Surface Antigen Seroclearance.

Hepatitis B surface antigen (HBsAg) seroclearance has been recommended as an optimal endpoint of antiviral treatment by the latest chronic hepatitis B management guideline.1 However, few reports investigated the durability of response after HBsAg seroclearance, because of a lower HBsAg seroclearance rate and the difficulty of obtaining a sufficient number of samples for analysis. Our center has made a long-term commitment to investigate the personalized antiviral therapy for chronic hepatitis B. More than 300 patients achieved HBsAg seroclearance by interferon (IFN)-based antiviral treatment. In this study, the durability and the effects of hepatitis B virus (HBV) surface antibody (Anti-HBs) level on relapse after HBsAg seroclearance were investigated.

Prevalence and characteristics of hepatitis C virus infection in Shenyang City, Northeast China, and prediction of HCV RNA positivity according to serum anti-HCV level: retrospective review of hospital data.

OBJECTIVE: The prevalence of hepatitis C virus (HCV) infection is typically evaluated based on the current rate of positivity of anti-HCV antibody; however, HCV RNA positivity is considered the main criterion for antiviral treatment of HCV infection in the clinical setting. In this study, we evaluated the prevalence of HCV infection based on anti-HCV and HCV RNA detection in the population of Liaoning Province, and investigated the correlation between serum HCV RNA positivity and anti-HCV levels. METHODS: A total of 192,202 patients who underwent serum anti-HCV examination at Shengjing Hospital in 2018 were enrolled in the study. Anti-HCV production was tested using a chemiluminescence assay, and serum HCV RNA detection was performed with Roche COBAS TaqMan (CTM) Analyzer. RESULTS: The prevalence of anti-HCV was 1.21 and 0.93% among male and female patients in Liaoning Province, respectively. The positive rates of anti-HCV and serum anti-HCV levels were both age-related, in which patients over 40 years of age had a significantly higher anti-HCV positive rate than those younger than 40 years. Among the anti-HCV-positive patients, the average HCV RNA positive rate was 51.66 and 35.93% in males and females, respectively. Spearman rank analysis showed a significantly positive correlation between serum HCV RNA positivity and the level of anti-HCV. The best cut-off value using serum anti-HCV levels to predict the positivity of HCV RNA was determined to be 9.19 signal-to-cut-off ratio (s/co) in males and 10.18 s/co in females. CONCLUSION: The prevalence of anti-HCV in the general population of Liaoning Province was around 1.04%, which was higher than that previously reported from a national survey of HCV infection in China. Approximately 42.9% of the anti-HCV-positive patients also tested positive for HCV RNA. However, the positive correlation between the serum anti-HCV and HCV RNA levels suggests that the positivity of serum HCV RNA can be predicted according to the anti-HCV level in anti-HCV-positive patients, which can improve screening and facilitate timely intervention to prevent the spread of infection.

AKR1B10 Inhibitor Epalrestat Facilitates Sorafenib-Induced Apoptosis and Autophagy Via Targeting the mTOR Pathway in Hepatocellular Carcinoma.

Sorafenib is the standard systemic treatment for advanced hepatocellular carcinoma (HCC), and improving its therapeutic effects is crucial for addressing cancer aggression. We previously reported that epalrestat, an aldo-keto reductase 1B10 inhibitor, enhanced sorafenib's inhibitory effects on HCC xenograft in nude mice. This study aimed to elucidate the mechanism of epalrestat's anti-tumour enhancing effects on sorafenib. HepG2 cells were treated with sorafenib, epalrestat, and their combination. Cell proliferation was assessed with Cell Counting Kit-8 and colony formation assays. AKR1B10 supernate concentration and enzyme activity were detected by ELISA assay and the decrease of optical density of NADPH at 340 nm. Cell cycle and apoptosis analyses were performed with flow cytometry. Western blots clarified the molecular mechanism underlying effects on cell cycle, apoptosis, and autophagy. The anti-tumour mechanism was then validated in vivo through TUNEL and immunohistochemistry staining of HCC xenograft sections. Epalrestat combined with sorafenib inhibited HepG2 cellular proliferation in vitro, arrested the cell cycle at G0/G1, and promoted apoptosis and autophagy. Treatment with a specific mTOR activator MHY-1485 increased mTOR phosphorylation, while suppressing apoptosis and autophagy. Consistent with in vitro results, data from the HCC-xenograft nude mouse model also indicated that combined treatment inhibited the mTOR pathway and promoted apoptosis and autophagy. In conclusion, epalrestat heightens sorafenib's anti-cancer effects via blocking the mTOR pathway, thus inducing cell cycle arrest, apoptosis, and autophagy.

A molecularly imprinted polymer based chemiluminescence array sensor for one-step determination of phenothiazines and benzodiazepines in pig urine.

The residues of phenothiazines and benzodiazepines in foods of animal origin are dangerous to consumers. For inspection of their abuses, this study for the first time reported on the use of a chemiluminescence array sensor for the simultaneous determination of four phenothiazines and five benzodiazepines in pig urine. Two molecularly imprinted polymers were coated in different wells of a conventional 96-well microtiter plate as the recognition reagents. After sample loading, the absorbed analytes were initiated directly by using an imidazole enhanced bis(2,4,6-trichlorophenyl)oxalate-hydrogen peroxide system to emit light. The assay process consisted of only one sample-loading step prior to data acquisition, so one test was finished within 10 min. The limits of detection for the nine drugs in the pig urine were in a range of 0.1 to 0.6 pg/mL, and the recoveries from the fortified blank urine samples were in a range of 80.3 to 95%. Furthermore, the sensor could be reused six times. Therefore, this sensor could be used as a simple, rapid, sensitive and reusable tool for routine screening for residues of phenothiazines and benzodiazepines in pig urine.

Molecularly imprinted polymer based microtiter chemiluminescence array for determination of phenothiazines and benzodiazepines in pork.

In this study, a molecularly imprinted polymer based chemiluminescence array capable of simultaneous determining phenothiazines and benzodiazepines was first reported. Two polymers were coated in different wells of the conventional 96-well microtiter plate as the recognition reagents, and the added analytes competed with a horseradish peroxidase-labeled bi-hapten conjugate to bind the recognition reagents. The light signal was induced by using a highly effective luminol-H2O2-IMP system. The assay procedure consisted of only one sample-loading step prior to data acquisition. Then, the array was used to determine 4 phenothiazines and 5 benzodiazepines in pork simultaneously. The limits of detection for the 9 drugs were in a range of 0.001-0.01 ng/mL, and the recoveries from the fortified blank pork were in a range of 63.5%-94.1%. Furthermore, the array could be reused for 8 times. The detection results for some real pork samples were consistent with an ultra performance liquid chromatography method.

Complement factor 3 among children with hepatitis A: Assessment of bilirubin levels.

OBJECTIVE: To evaluate the complement factor 3 levels in children with hepatitis A. METHODS: This observational study was conducted at the Infectious Diseases Hospital of Hotan District, China, from September 2014 to January 2015, and comprised children with hepatitis A and controls. The patients were divided into two groups. The ones with total bilirubin less than or equal to 2mg/dl comprised group A, while the ones whose total bilirubin was more than 2mg/dl was named group B. Besides, we enrolled age- and gender-matched healthy children as controls. SPSS 13 was used for data analysis. RESULTS: Of the 100 participants, 41(41%) were in group A, 29(29%) in group B and 30(30%) were controls. The serum level of alanine aminotransferase, aspartate aminotransferase, total bile acid, the incidence of ascites and the incidence of hepatic encephalopathy were significantly increased in patients of group B when compared to group A (p=0.046, p=0.009, p<0.0001, p=0.018 and p=0.026). The levels of prothrombin time activity, total protein and albumin were higher in group A (p<0.0001, p<0.0001, and p <0.0001). Total hepatitis A patients had significantly lower serum complement factor 3 levels compared to normal controls (p =0.018). Group B had significantly lower serum complement factor 3 levels compared to normal controls (p <0.0001) and group A (p<0.0001). In total patients, complement factor 3 levels were negatively correlated with total bilirubin and alanine aminotransferase (p=0.029), while complement factor 3 levels were positively correlated with prothrombin time activity (p=0.001). CONCLUSIONS: Complement factor 3 values were found to be decreased in children hospitalised with hyperbilirubinaemia hepatitis A.

Virtual mutation and directional evolution of anti-amoxicillin ScFv antibody for immunoassay of penicillins in milk.

In this study, an anti-amoxicillin single chain variable fragment (ScFv) antibody was evolved by directional mutagenesis of a contact amino acid residue based on the analysis of virtual mutation. Comparison with its parental ScFv, the mutant showed highly improved affinity for 11 penicillins with up to 6-folds increased sensitivity. Then, its recognition mechanisms for the 11 drugs were studied by using molecular docking. Results showed that the mutant-penicillins intermolecular forces increased and the total binding energies decreased dramatically, which were responsible for the improvement of antibody sensitivity. The ScFv mutant was used to develop an indirect competitive enzyme linked immunosorbent assay for determination of the 11 drugs in milk. The limits of detection were in the range of 0.2-3.0 ng/mL, the crossreactivities were in the range of 31%-132%, and the recoveries from standards fortified blank milk were in the range of 65.7%-92.4%. This is the first study reporting the directional evolution of a ScFv antibody based on virtual mutation and the use of ScFv antibody for determination of penicillins in foods of animal origin.

Transport characteristics of nanoscale zero-valent iron carried by three different "vehicles" in porous media.

This study investigated the transport properties of nanoscale zero-valent iron (Fe(0)) (nZVI) carried by three vehicles: water, sodium dodecyl sulfate (SDS) solution, and SDS foam. Batch experiments were conducted to assess the sedimentation capability of nZVI particles in these three vehicles. Column experiments were conducted to investigate the transport properties of nZVI in porous media formed with different sizes of sand (0.25 mm to 0.5 mm, 0.5 mm to 0.9 mm, and 0.9 mm to 1.4 mm). Three main results were obtained. First, the batch experiments revealed that the stabilities of nZVI particles in SDS solution and SDS foam were improved, compared with that of nZVI particles in water. Moreover, the sedimentation of nZVI in foam was closely associated with the foam drainage volume. The nZVI content in foam was similar to that in the original foaming suspension, and the nZVI particle distribution in foam became significantly more uniform at a stirring speed of 3000 r/min. Second, the transport of nZVI was enhanced by foam compared with water and SDS solution for 0.25 mm to 0.5 mm diameter sand. For sand with diameters of 0.5 mm to 0.9 mm and 0.9 mm to 1.4 mm, the mobility of nZVI carried by SDS solution was optimal, followed by that of nZVI carried by foam and water. Thus, the mobility of nZVI in finer sand was significantly enhanced by foam, compared with that in coarse sand. In contrast, compared with the bare nZVI suspension and nZVI-laden foam, the spatial distribution of nZVI particles carried by SDS solution was significantly uniform along the column length. Third, the SDS concentration significantly influenced the migration of nZVI in porous media. The enhancement in the migration of nZVI carried by SDS solution was greater at an SDS dose of 0.25% compared with that at the other three doses (0.2%, 0.5%, and 1%) for sand with a 0.25 mm to 0.5 mm diameter. Increased SDS concentrations positively affected the transport of nZVI by foam for sand with a 0.25 mm to 0.5 mm diameter, and the SDS concentrations for enhancing the mobility of nZVI carried by SDS foam satisfied the following order: 1% > 0.5% > 0.25% > 0.2%. Thus, SDS solution and SDS foam were better vehicles than water for delivering nZVI particles to porous media for contamination remediation.

Intrapleural perfusion hyperthermia improves the efficiency of anti­PD1 antibody­based therapy for lung adenocarcinoma: A case report.

Chemotherapy based on intrapleural perfusion hyperthermia (IPH) can markedly improve the sensitivity of lung adenocarcinoma cells to anti-programmed cell death receptor 1 (PD1) antibody adjuvant chemotherapy and enhance the clinical response of a patient. In the present study, a unique case of a patient who failed to respond to immunotherapy combined with chemotherapy but achieved prolonged stable disease after treatment with IPH and subsequent sintilimab-based treatment, is reported. A 50-year-old Chinese female patient was admitted to a regional cancer hospital presenting with hemoptysis and persistent fever. The findings of computed tomography imaging and thoracic puncture tissue biopsy indicated a diagnosis of adenocarcinoma. The TNM and clinical stage were identified as cT2N3M0 and stage IIIB, respectively. Immunohistochemical tests showed the expression of programmed death-ligand 1 (PD-L1) with a tumor proportion score of 2%. No other classic genetic alterations were detected. Initially, sintilimab-based chemotherapy at 200 mg was administered, for three cycles from April 2020, and increased pleural effusion was observed on the left side. The best overall response (BOR) assessment of the local lesion was progressive disease. IPH combined with chemotherapy was then carried out from August to September 2020, after which the same course of sintilimab-based chemotherapy as aforementioned was provided from October 2020 to September 2023. The BOR evaluation results during the monotherapy courses were all judged as stable disease. Therefore, it was concluded that IPH can substantially improve the efficiency of anti-PD1 antibody-based therapy for lung adenocarcinoma.

Muscle function is superior to muscle mass in predicting 90-day mortality in patients with acute-on-chronic liver failure: A prospective study.

OBJECTIVES: Low muscle mass has been found to be associated with adverse outcomes in patients with acute-on-chronic liver failure. However, data regarding the prognostic role of low muscle function are limited. Therefore, we aimed to investigate the predictive effect of low muscle function on 90-d mortality in patients with acute-on-chronic liver failure. METHODS: This prospective study consecutively enrolled acute-on-chronic liver failure patients from March 2021 to October 2022. Muscle function was assessed using the liver frailty index, and the time-dependent receiver operating characteristic curve with the highest Youden index was used to determine the optimal cutoff values of liver frailty index for diagnosing low muscle function. RESULTS: The study included 126 acute-on-chronic liver failure patients. The median liver frailty index was 3.89 (0.83), with 51 (40.5) patients classified as having low muscle function. Multivariate Cox analysis identified low muscle function (hazard ratio = 4.309; 95% CI, 1.795-10.345; P = 0.001) and number of organ failures (hazard ratio = 4.202; 95% CI, 2.040-8.656; P < 0.001) as independent risk factors for 90-d mortality. However, the multivariate analysis did not retain the significant effect of low muscle mass. Furthermore, multivariable logistic analysis revealed that age (odds ratio = 1.042; 95% CI, 1.002-1.083; P = 0.038), organ failures (odds ratio = 2.572; 95% CI, 1.331-4.968; P = 0.005), and low muscle mass (odds ratio = 6.607; 95% CI, 2.579-16.927; P < 0.001) were independent risk factors for low muscle function. CONCLUSIONS: The prognostic value of low muscle function was found superior to that of low muscle mass in patients with acute-on-chronic liver failure. Therefore, it is important to assess the muscle function and develop potential targeted treatment strategies in this population.

Association of myosteatosis with short-term outcomes in patients with acute-on-chronic liver failure.

Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray's competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000-1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312-1.710, P < 0.001), and sarcopenia (HR 1.802, 95% CI 1.062-3.060, P = 0.029) were independently associated with increased 90-day mortality. Subgroup analysis of male patients with HBV-ACLF revealed that myosteatosis (HR 2.119, 95% CI 1.101-4.078, P = 0.025) was promising prognostic factors for 90-day mortality after being adjusted for ascites, acute kidney injury, AARC score, and sarcopenia. Myosteatosis is predictive of short-term outcomes in male patients with HBV-ACLF. Our results emphasise the importance of focusing on muscle fat infiltration in patients with HBV-ACLF. Further studies are warranted to investigate the underlying mechanisms and potential therapies for myosteatosis.

Excessive fluoride induces ovarian function impairment by regulating levels of ferroptosis in fluorosis women and ovarian granulosa cells.

The aim of this study was to investigate the role of ferroptosis in fluorosis women and the in vitro molecular mechanisms leading to ovarian dysfunction and abnormal hormone secretion by sodium fluoride (NaF) treatment of KGN cells. Fifty women with fluorosis as Fluorosis group and fifty healthy women as Control group were included in this study. The levels of lipid peroxidation and activities of antioxidant enzyme were assessed by photometric methods. The content of iron and glutathione (GSH) in serum was measured by microplate method. KGN cells were treated by different concentration of NaF (0, 1, 2, 4 and 8 ×10-3 M) for 24 h. The mRNA and protein expression levels of ferroptosis-related molecules, including glutathione peroxidase 4 (GPX4), solute carrier family 7 member (SLC7A11), nuclear factor erythroid 2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1) and p53, were assessed by qRT-PCR and western blot analysis. Fluorosis group women had a significant higher levels of iron, Malondialdehyde (MDA), FSH and LH, and a lower levels of E2 and antioxidant enzyme in serum than that in the control group. The representative molecular changes of ferroptosis, such as the decrease in GPX4, Nrf2 and SLC7A11 expression (mRNA and protein expression), the increase in protein expression of p53, and a reduced level of E2 were observed in KGN cells treated by excessive NaF.It is concluded therefore that NaF increases the expression of p53 and inhibits ovarian granulosa cell ferroptosis preventive protein expression, resulting in abnormal hormone secretion and the ovarian dysfunction.

Prediction Model for the Clearance of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B before Interferon Therapy: A Prospective Case-Control Study.

To evaluate the prediction model comprised of patients' laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case-control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030-0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768-71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006-0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040-0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138-13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.