[Molecular characteristics and drug susceptibility analysis of Streptococcus agalactiae from respiratory specimen sources].

To study the carriage status of drug susceptibility, clonal complex groups, serotypes, surface proteins and virulence genes of Streptococcus agalactiae from respiratory specimen sources. A total of 35 strains of S.agalactiae meeting the criteria were collected from 3 hospitals in 2 locations, Tangshan and Jinan. The age span of the patients was 3 days-92 years, and the percentage of elderly patients≥60 years was 71.5%.The susceptibility to 9 antimicrobial drugs was measured and analyzed using the micro broth dilution method. The strains were 100.0% sensitive to penicillin, linezolid, vancomycin, and ceftriaxone; However, it exhibits high resistance rates to erythromycin, clindamycin and levofloxacin, at 97.1%, 85.7% and 82.9% respectively; and the resistance rates to tetracycline and chloramphenicol were 34.3% and 14.2%, respectively. Genome sequence determination and analysis showed that 16 resistance genes were detected in 35 strains, among which: macrolide and lincosamide resistance genes were mainly ermB, with a carrying rate of 74.2%; tetracycline resistance genes were mainly tetM, with a carrying rate of 25.7%; in addition, the mutation rates of the quinolone resistance determinants gyrA and parC were 88.5% and 85.7%, respectively. 35 strains belonged to 6 ST types and 4 clonal groups, with CC10/ST10 as the main one, accounting for 62.8%; they contained 4 serotypes of Ⅰb, Ⅱ, Ⅲ, and Ⅴ, as well as 1 untyped strain, with serotype Ⅰb as the main one, accounting for 65.7%. The strains carried three pilus types, PI1+PI2a, PI2a and PI2b types, respectively, and detected five surface proteins, alpha, alp1, rib, srr, and rdf_0594, and seven virulence factors, cba, cfb, cylE, fbsA, hylB, lmb, and pavA. Overall, S.agalactiae isolated from respiratory tract specimens is predominantly sourced from elderly patients, with CC10 strains being most prevalent. These strains harbor multiple drug-resistant and virulence genes, demonstrating elevated resistance rates to macrolides, lincosamides, and quinolones. This emphasizes the necessity for vigilant attention to the health threat posed by S. agalactiae from respiratory tract speciments of elderly patients.

[Research on the mechanism of shengxian and jinshuiliujun decoction in treating silicosis based on network pharmacology].

Objective: To explore the active ingredients of shengxian and jinshuiliujun decoction with the method of network pharmacology, and to verify the experimental mechanism of its treatment of silicosis. Methods: In May 2023, the active ingredients and targets of drugs in shengxian and jinshuiliujun decoction were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database. The target of silicosis disease was screened by databases such as Genecards, Disease Gene Network (DisGeNET), Comparative Toxicogenomics Database (CTD), etc. The screened drug targets and disease targets were intersected to obtain the target set of shengxian and jinshuiliujun decoction for the treatment of silicosis. Protein-protein interaction (PPI) network analysis was performed on the target set through STRING database, and core target genes were screened. GO enrichment analysis and KEGG pathway analysis of intersection genes were performed based on Metascape database, and molecular docking verification of key components and targets of shengxian and jinshuiliujun decoction was carried out. Twenty-four adult male SD rats with SPF grade were randomly divided into control group, model group and TCM intervention group, with 8 rats in each group. The dust-stained rat model was prepared by non-tracheal exposure of 1 ml silica suspension (50 mg/ml) in one go, and TCM intervention group was given shengxian and jinshuiliujun decoction[6 g/ (kg·d) ] on the second day. The CT of the lungs of each group was observed 28 days after the dust-stained rat model. Paraffin sections of rat lung tissues were prepared and stained with Hematoxylin-Eosin (HE) and Masson. Western blot was used to verify the expression of core target-related proteins in rat lung tissues after the intervention of shengxian and jinshuiliujun decoction for 28 days, and the differences in protein expression between groups were compared by one-way analysis of variance. Results: A total of 205 active ingredients and 3345 active compounds were selected from shengxian and jinshuiliujun decoction, corresponding to 281 targets, among which 240 targets were related to silicosis. Serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), tumor necrosis factor (TNF) and interleukin (IL) 6 may be the key targets of shengxian and jinshuiliujun decoction in the treatment of silicosis. Through enrichment analysis, 30 GO entries and 20 potential signaling pathways were screened according to P-value, including nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK) and cancer signaling pathways. Molecular docking showed that the active compounds of shengxian and jinshuiliujun decoction had good binding with the core target proteins, and the strongest binding properties were beta-sitosterol and TNF-α (-10.45 kcal/mol). In animal experiments, the inflammatory infiltration and fibrosis of lung tissue of rats in TCM intervention group were significantly improved. Compared with control group, the levels of TNF-α, IL-1ß, IL-6 and NF-κB in lung tissue of model group were significantly increased (P<0.05). Compared with model group, the lung injury of rats in TCM intervention group was significantly improved, and the expressions of TNF-α, IL-1ß, IL-6 and NF-κB were significantly decreased (P<0.05) . Conclusion: Shengxian and jinshuiliujun decoction in the treatment of silicosis may play an anti-fibrosis role by inhibiting the NF-κB signal transduction pathway mediated by inflammatory factors such as TNF-α and IL-1ß, which provides a reference for further exploring the material basis and mechanism of its action.

[Overview and inspiration of WHO Guidelines on mental health at work].

The World Health Organization (WHO) released the Guidelines on mental health at work and published a related ILO/WHO joint policy brief with the International Labor Organization (ILO) on September 28th, 2022. They called on governments and employers to adopt supportive interventions in the fields of mental health and occupational health to protect and promote workers' mental health. Based on these two publications, this article summarizes the main ideas of the guidelines, and reviews the relevant legislation progress of China and international level. Besides, it proposes suggestions for formulating occupational safety and health policies, and promoting mental health at work.

Introduction and validation of the open symptom framework: a public domain modular framework for patient-reported measurement of symptoms related to cancer and its treatment.

PURPOSE: We provide an initial description and validation of some public domain patient-reported outcome (PRO) items to assess cancer symptom burden to address immediate barriers to symptom assessment use in clinical practice and facilitate future research. METHODS: We created the Open Symptom Framework (OSF), a flexible tool for clinical cancer-related symptom assessment. The items comprise six components: recall period, concept, symptom, qualifier(s), a definition, and a 5-point Likert-type response. We recruited patients receiving cancer therapy in the United States and United Kingdom. We assessed external construct validity by comparing OSF scores to the PRO-CTCAE measure and assessed reliability, scalability, dimensionality, and item ordering within a non-parametric item response theory framework. We tested differential item functioning for country, age, gender, and level of education. RESULTS: We developed a framework alongside clinical and psychometric experts and debrieifed with 10 patients. For validation, we recruited 331patients. All items correlated with the PRO-CTCAE equivalents (r = 0.55-0.96, all p < 0.01). Mokken analysis confirmed the scalability and unidimensionality of all symptom scales with multiple items at the scale (Ho = 0.61-0.75) and item level (Hi = 0.60-0.76). Items are interpreted consistently between demographic groups (Crit = 0 for all groups). CONCLUSION: The public domain OSF has excellent psychometric properties including face, content, and criterion validity and can facilitate the development of flexible, robust measurements to fulfil stakeholder need. The OSF was designed specifically to support clinical assessment but will function well for research. Further work is planned to increase the number of symptoms and number of questions per symptom within the framework.

[Analysis of the molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae in a hospital in Hunan Province].

To examine the molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the horizontal transmission of blaKPC and blaNDM genes for the prevention and treatment of CRKP. A total of 49 clinically isolated CRKP strains were retrospectively analyzed from January to December 2022 at The First Hospital of Hunan University of Chinese Medicine. Phenotypic screening was performed using modified carbapenem inactivation assay (mCIM) and EDTA-carbapenem inactivation assay (eCIM). Polymerase chain reaction (PCR) was utilized to identify carbapenem resistance genes, ß-lactamase resistance genes, and virulence genes, while multi-locus sequence analysis (MLST) was employed to assess the homology of CRKP strains. Conjugation experiments were conducted to infer the horizontal transmission mechanism of blaKPC and blaNDM genes. The results showed that the study included 49 CRKP strains, with 44 carrying blaKPC and 8 carrying blaNDM, Three strains were identified as blaKPC+blaNDM-CRKP. In this study, 28 out of 49 CRKP strains (57.2%) were found to carry virulence genes. Additionally, one CRKP strain tested positive in the string test and was found to carry both Aerobactin and rmpA virulence genes. MLST results revealed a total of 5 ST types, with ST11 being predominant (41/49, 83.7%). Successful conjugation was observed in all 3 blaKPC-CRKP strains, while only 1 out of 3 blaNDM-CRKP strains showed successful conjugation. The transconjugant exhibited significantly reduced susceptibility to imipenem and cephalosporin antibiotics. In conclusion, the resistance mechanism of CRKP in this study is primarily attributed to the production of KPC enzymes, along with the presence of multiple ß-lactamase resistance genes. Additionally, there is a local prevalence of hv-CRKP and blaKPC+blaNDM-CRKP. blaKPC and blaNDM can be horizontally transmitted through plasmids, with varying efficiency among different strains.

Allicin in pregnancy diets modulates steroid metabolism in pregnant sows and placental sulphate metabolism promoting placental angiogenesis and foetal development.

The low-birth-weight of piglets is an important factor affecting pig enterprises. The placenta, as a key organ for material exchange between mother and foetus, directly influences the growth and development of the foetus. Allicin exhibits various biological activities, including anti-inflammatory and antioxidant properties. It may also play a crucial role in enhancing sow reproductive performance and placental angiogenesis. In this study, we used 70 lactating Landrace × Yorkshire binary heterozygous sows to explore the effect of allicin on the reproductive performance of sows and placental development. The sows were randomly assigned into the Allicin group (Allicin), which was fed with a diet containing 0.25% allicin, and the negative control group, which was fed with basal feed. The experimental period lasted for 114 d from the date of mating to the end of farrowing. The results showed that the addition of allicin to the gestation diets increased the number of total born piglets, born alive piglets, and high-birth-weight piglets, reduced peripartum oxidative stress, alleviated dysregulation of glucose-lipid metabolism in sows, and increased the levels of antioxidant markers in the placenta. Differential analysis of metabolites in maternal plasma and placenta samples by non-targeted metabolomics revealed that allicin improved cholesterol metabolism, steroid biosynthesis, and increased plasma progesterone levels in sows. Allicin promoted sulphur metabolism, cysteine and methionine metabolism in placental samples and increased the hydrogen sulphide (H2S) content in the placenta. In addition, Quantitative Real-time PCR, Western blot and immunofluorescence results showed that allicin upregulated the expression of angiogenesis-related genes, VEGF-A, FLK 1 and Ang 1, in the placenta, implying that it promoted placental angiogenesis. These results indicate that supplementing the diet of pregnant sows with allicin reduces oxidative stress, alleviates dysregulation of glucose-lipid metabolism during the periparturient period, and promotes placental angiogenesis and foetal development by increasing plasma progesterone level and placental H2S content.

Adherence to the EAT-Lancet diet reduces the risk of head and neck cancers in 101,755 American adults: a prospective cohort study.

OBJECTIVES: The aim of this study was to explore the relationship between the EAT-Lancet diet (ELD) and head and neck cancers (HNCs) in 101,755 Americans enrolled in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. STUDY DESIGN: Prospective cohort study. METHODS: ELD score was calculated to assess participant's adherence to ELD. Cox hazard regression models were utilised to evaluate the association of ELD and dietary components with HNC risk. Restricted cubic spline (RCS) plots were employed to explore the linearity of the relationships. Predefined subgroup analyses and sensitivity analyses were performed to identify potential effect modifiers and to assess the stability of the findings, respectively. RESULTS: After a mean follow-up of 8.84 years, 279 cases of HNCs, including 169 cases of oral cavity and pharyngeal cancers and 110 cases of laryngeal cancer were recorded. This study observed a dose-response negative correlation between ELD and HNCs (hazard ratio [HR]Q4 vs Q1: 0.52; 95% confidence interval [CI]: 0.34, 0.80; P-trend = 0.003; HRper SD increment: 0.80; 95% CI: 0.71, 0.91), and oral cavity and pharyngeal cancers (HRQ4 vs Q1: 0.52; 95% CI: 0.31, 0.88; P-trend = 0.008; HRper SD increment: 0.78; 95% CI: 0.66, 0.92). Analysis using RCS plots indicated a significant linear association between adherence to the ELD and reduced risk of HNCs and oral cavity and pharyngeal cancers (P-nonlinearity > 0.05). Subgroup analysis did not reveal significant interaction factors (P-interaction > 0.05), and sensitivity analysis confirmed the robustness of this study. Additionally, negative correlations were found between the consumption of fruits and whole grains and HNCs (fruits: HRQ4 vs Q1: 0.58; 95% CI: 0.40, 0.84; P-trend = 0.010; whole grains: HRQ4 vs Q1: 0.51; 95% CI: 0.26, 0.97; P-trend = 0.004). CONCLUSION: Adherence to ELD contributes to the prevention of HNCs.

[Association between body composition and coronary artery calcification in patients with chronic kidney disease].

Objective: To investigate the association between body composition and coronary artery calcification in patients with chronic kidney disease (CKD). Methods: This cross-sectional study enrolled patients with CKD hospitalized from May 2019 to April 2022 at Sun Yat-sen Memorial Hospital, Guangzhou, China. Skeletal muscle mass index and visceral fat area were measured by bioelectrical impedance analysis. Coronary artery calcification was assessed by computed tomography. Patients were divided into coronary artery calcification group and non-coronary artery calcification group according to the incidence of coronary artery calcification. Patients were categorized into tertile groups according to their skeletal muscle mass index and visceral fat area levels ranging from the lowest to the highest levels (T1 to T3). We defined skeletal muscle mass index≤30.4% as low muscle mass and visceral fat area≥80.6 cm2 as high visceral fat based on the results of the restricted cubic spline graph. All individuals were divided into 4 phenotypes: normal body composition, low muscle mass, high visceral fat, and low muscle mass with high visceral fat. Spearman correlation analysis and logistic regression analysis were used to assess the association between skeletal muscle mass index, visceral fat area and coronary artery calcification. Results: A total of 107 patients with CKD were enrolled, with an age of (60.0±14.1) years, including 41 female patients (38.3%). Patients of coronary artery calcification group had lower skeletal muscle mass index ((32.0±4.8) vs. (34.3±4.8), P=0.016) and higher visceral fat area ((70.8±32.6) cm2 vs. (47.9±23.8) cm2, P<0.001) than those of non-coronary artery calcification group. Patients in the T3 group of skeletal muscle mass index had a lower prevalence of coronary artery calcification (17 (48.6%) vs. 28 (77.8%)) and a lower coronary artery calcification score (0.5 (0, 124.0) vs. 12.0 (0.3, 131.0)) than those in the T1 group (P<0.05). Similarly, patients in the T1 group of visceral fat area had a lower prevalence of coronary artery calcification (14 (40.0%) vs. 29 (80.6%)) and a lower coronary artery calcification score (0 (0, 3.0) vs. 37.0 (2.0, 131.0)) than those in the T3 group (P<0.05). Likewise, patients with both low muscle mass and low muscle mass with high visceral fat had a higher prevalence of coronary artery calcification (11(78.6%) vs. 33 (47.8%); 15 (83.3%) vs. 33 (47.8%)) and a higher coronary artery calcification score (31.1 (0.8, 175.8) vs. 0 (0, 16.4); 27.6 (6.4, 211.4) vs. 0 (0, 16.4)) than those with normal body composition (P<0.05). Spearman correlation analysis showed that skeletal muscle mass index was inversely correlated with coronary artery calcification score (r=-0.212, P=0.028), and visceral fat area was positively correlated with coronary artery calcification score (r=0.408, P<0.001). Multivariate logistic regression analysis showed that increased skeletal muscle mass index was inversely associated with coronary artery calcification prevalence (T2: OR=0.208, 95%CI: 0.056-0.770, P=0.019; T3: OR=0.195, 95%CI: 0.043-0.887, P=0.034), and reduced visceral fat area was inversely associated with coronary artery calcification prevalence (T1: OR=0.256, 95%CI: 0.071-0.923, P=0.037; T2: OR=0.263, 95%CI: 0.078-0.888, P=0.031). Consistently, both low muscle mass and low muscle mass with high visceral fat were associated with coronary artery calcification prevalence (OR=6.616, 95%CI: 1.383-31.656, P=0.018; OR=5.548, 95%CI: 1.062-28.973, P=0.042). Conclusion: Reduced skeletal muscle mass index and increased visceral fat area are significantly associated with both the prevalence and severity of coronary artery calcification in patients with CKD.

[Predict the effect of the number of positive preoperative serum tumor markers on the surgical method and prognosis of intrahepatic cholangiocarcinoma patients based on mediation analysis].

Objective: To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma. Methods: This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect. Results: Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (ß=-0.092, P=0.039),and had a positive predictive effect on the surgical method (ß=0.244,P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma (ß=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions: The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Outcome of serial cardiac evaluations during doxorubicin-based chemotherapy in small- to medium-sized dogs with multicentric lymphoma.

Doxorubicin is an anthracycline antitumor antibiotic with dose-dependent and cumulative cardiotoxicity. However, the necessity for serial cardiac evaluation is unknown in dogs without risk factors for dilated cardiomyopathy (DCM). This study aimed to investigate serial changes in echocardiographic and electrocardiographic measures in small- and medium-sized dogs after four doxorubicin doses. We included 17 dogs, weighting < 20 kg, with multicentric lymphoma. All dogs received doxorubicin over 30 min every 4 weeks as part of a multi-drug chemotherapy protocol. The average doxorubicin dose was 3.8 times per dog. Clinical cardiotoxicity was not observed during the monitoring period. The incidence of developing arrhythmia was not significantly associated with the number of doxorubicin doses received (P = 0.600). The development of valvular regurgitations and mitral regurgitation in these dogs was not significantly associated with the number of doxorubicin doses (P = 0.363 and P = 0.779, respectively). The other echocardiographic results were not significantly different between each evaluation. In conclusion, our results showed no significant cardiotoxicity under echocardiogram and electrocardiogram in small- and medium-sized dogs without risk factors for DCM after four doses of doxorubicin in a 30-minute infusion method.

[Minimally invasive treatments and open joint surgery for disorders of the temporomandibular joint]. / Minimaal invasieve behandelingen en opengewrichtschirurgie voor aandoeningen van het kaakgewricht.

The initial treatment of symptomatic disorders of the temporomandibular joint typically consists of a conservative approach, in which medication (painkillers and muscle relaxants), orofacial physiotherapy and splints are most important. In most cases, minimally invasive treatment options, such as arthrocentesis, arthroscopy or joint injections, are only considered when conservative methods provide insufficient symptom reduction. There is, however, an ongoing debate about the optimal treatment strategy due to an increasing body of evidence concerning the superior effectiveness in symptom reduction of minimally invasive treatment options with regard to conservative treatments. If these minimally invasive treatment options are also ineffective, open joint surgery may be considered as a last option for a select group of patients.

[Clinical analysis of 18 children with aggressive mature B-cell lymphoma after liver transplantation].

Objective: To summarize the clinical characteristics, prognostic factors and treatment outcomes of childhood aggressive mature B-cell lymphoma after liver transplantation. Methods: This retrospective study included 18 children with newly diagnosed aggressive mature B-cell lymphoma after liver transplantation and treated from June 2018 to June 2022 in the Department of Hematology and Oncology of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine. Clinical characteristics, treatment and outcomes of patients at last evaluation were analyzed. Overall survival (OS) and event free survival (EFS) rates were calculated by Kaplan-Meier method and Log-Rank analysis was performed to find factors of poor prognosis. Results: Among all 18 patients, there were 6 males and 12 females, and the age of onset was 40 (35, 54) months. The interval from transplant to tumor diagnosis was 21 (17, 35) months and 5 patients had early onset disease (<1 year since transplant). Seventeen patients had abdominal lesions. Diarrhea, vomiting and abdominal masses were the main clinical manifestations. All patients were Epstein-Barr virus (EBV) related posttransplant lymphoproliferative disorders (PTLD). One patient received individualized therapy due to critical sick at diagnosis, and the remaining 17 patients received CP (cyclophosphamide, methylprednisolone plus rituximab) and (or) modified EPOCH (prednisone, etoposide, doxorubicin, vincristine, cyclophosphamide plus rituximab) regimens. Of all 18 patients, 15 cases got complete response, 2 cases got partial response, 1 patient died of severe infection. The 2-year OS and EFS rates of 18 patients were (94±5)% and (83±8)%, respectively. None of age, gender or early onset disease had effect on OS and EFS rates in univariate analysis (all P>0.05). Conclusions: The symptoms of PTLD were atypical. Close surveillance of EBV-DNA for patients after liver transplantation was crucial to early stage PTLD diagnosis. CP or modified EPOCH regimen was efficient for pediatric patients with aggressive mature B cell lymphoma after liver transplantation.

PINK1/Park2-Mediated Mitophagy Relieve Non-Alcoholic Fatty Liver Disease.

Up to now, there's a limited number of studies on the relationship between PINK1/Park2 pathway and mitophagy in NAFLD. To investigate the effect of Park2-mediated mitophagy on non-alcoholic fatty liver disease (NAFLD). Oleic acid was used for the establishment of NAFLD model. Oil red-dyed lipid drops and mitochondrial alternations were observed by transmission electron microscopy. Enzymatic kit was used to test lipid content. The levels of IL-8 and TNF-alpha were determined by ELISA. Lenti-Park2 and Park2-siRNA were designed to upregulate and downregulate Park2 expression, respectively. The changing expression of PINK and Park2 was detected by RT-qPCR and Western blot. Immunofluorescence staining was applied to measure the amount of LC3. Successful NAFLD modeling was featured by enhanced lipid accumulation, as well as the elevated total cholesterol (TC), triglyceride (TG), TNF-alpha and IL-8 levels. Mitochondria in NAFLD model were morphologically and functionally damaged. Park2 expression was upregulated by lenti-Park2 and downregulated through Park2-siRNA. The PINK1 expression showed the same trend as Park2 expression. Immunofluorescence staining demonstrated that the when Park2 was overexpressed, more LC3 protein on mitochondrial autophagosome membrane was detected, whereas Park2 knockdown impeded LC3' locating on the membrane. The transmission electron microscopy image exhibited that the extent of damage to the mitochondrial in NAFLD model was revered by enhanced Park2 expression but further exacerbated by reduced Park2 expression. Park2-mediated mitophagy could relive NAFLD and may be a novel therapeutic target for NAFLD treatment. Keywords: Non-alcoholic Fatty Liver Disease (NAFLD), Mitophagy, PINK1/Park2, Park2, PINK1.

Cryo-storage of porcine hides at the industrial scale for tissue engineering and regenerative medicine application.

BACKGROUND: The industrial scale cryo-storage of raw tissue materials requires a robust, low-cost and easy-to-operate method that can facilitate the down-stream process. OBJECTIVE: The study was aimed to develop the multifunctional protective solutions (MPS) for transportation at ambient conditions and also subsequent cryo-storage below -20 degree C of raw porcine hides for tissue engineering and regenerative medicine. MATERIALS AND METHODS: Protective solutions with antimicrobial activity and proteinase-inhibiting activity were developed and tested for its efficacy in preserving the extracellular matrix of porcine dermis from microbial spoilage, proteolytic degradation, freeze damage and excessive dehydration during shipping and cryo-storage. The MPSs contained phosphate-buffered saline with ethylene diamine tetra acetic acid (EDTA) added as chelator and proteinase inhibitor, as well as glycerol or maltodextrin (M180) as cryoprotectants. RESULTS: MPSs prepared with EDTA and glycerol or M180 had significant antimicrobial activity and proteinase-inhibiting activity during the period of shipping and handling. Glycerol and M180 prevented eutectic salt precipitation and excessive freeze dehydration upon cryo-storage of porcine hides. Without glycerol or M180, hides could be freeze-dehydrated to the low hydration at ~0.4 g/g dw, and formed irreversible plications after freezing. A critical hydration (0.8~0.9 g/g dw) was observed for the extracellular matrix of porcine dermis, and dehydration to a lower level could impose enormous stress and potential damage. The soaking of porcine hides in MPSs decreased water content as glycerol and M180 entered into dermis. Upon equilibration, the glycerol content in the tissue was about 94% of the incubating glycerol solution, but the M180 content in the tissue was only about 50% of the incubating M180 solution, indicating that M180 did not get into the entire aqueous domain within dermis. MPSs reduced ice formation and increased the unfrozen water content of porcine raw hides upon cryo-storage. CONCLUSION: MPSs prepared with EDTA and glycerol or M180 have antimicrobial activity and proteinase-inhibiting activity, which can be used for transportation and cryo-storage of raw hides at the industrial scale. Glycerol at 7.5% w/v and M180 at 20% w/v were sufficient to prevent freeze damage and excessive freeze dehydration. Doi.org/10.54680/fr24310110312.

Octenidine exposure was not associated with reduced octenidine susceptibility of meticillin-resistant Staphylococcus aureus in an extended-care facility in Singapore.

OBJECTIVES: Antiseptics such as chlorhexidine gluconate (CHG) and octenidine dihydrochloride (OCT) are frequently used in hospitals to prevent and control the transmission of meticillin-resistant Staphylococcus aureus (MRSA). Given the increasing prevalence of reduced CHG susceptibility of MRSA, there are concerns about the possibility of reduced OCT susceptibility. This study evaluated the prevalence of reduced CHG and OCT susceptibility over 3 years, and assessed the association between OCT exposure and reduced OCT susceptibility in MRSA. METHODS: MRSA isolates from inpatients who acquired MRSA in an extended-care facility between 2019 and 2021 were included in antiseptic susceptibility testing. Inpatients were exposed to universal daily CHG bathing from January to September 2019, and universal daily OCT bathing after October 2019. The minimum inhibitory concentrations (MICs) of CHG and OCT were determined using the broth microdilution method. Multi-variable logistic regression was used to assess if OCT exposure was independently associated with reduced OCT susceptibility. RESULTS: Of 186 isolates, 179 (96%) had reduced CHG susceptibility (MIC ≥4 mg/L) and 46 (25%) had reduced OCT susceptibility (MIC ≥2 mg/L). Reduced OCT susceptibility rates were 26.9%, 13.8% and 14.3% in 2019, 2020 and 2021, respectively. Reduced CHG susceptibility rates were 95.4%, 100% and 95.9% in 2019, 2020 and 2021, respectively. OCT exposure was not associated with reduced OCT susceptibility (adjusted odds ratio 0.23, 95% confidence interval 0.08-0.75; P=0.014), after adjusting for age, gender, race, year of sample collection, days at risk in facility, hospitalization in preceding year, and MRSA colonization/infection in preceding year. CONCLUSION: The prevalence of reduced OCT susceptibility has remained low, despite universal OCT bathing for extended inpatient care. However, the rate of reduced CHG susceptibility was high. OCT exposure was not associated with reduced OCT susceptibility in MRSA.

[A successfully treated case of respiratory failure caused by eating Nassariidaes].

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.

[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

[Prediction of prognosis of patients with radical resection of intrahepatic cholangiocarcinoma based on single cell omics].

Objectives: To analyze the survival benefit of intrahepatic cholangiocarcinoma (ICC) radical resection based on single cell omics. Methods: This is a retrospective case-series study. ICC single-cell sequencing was integrated from four data sets in the Gene Expression Omnibus Database, with a total of 46 patients undergoing radical resection, to explore the characteristics of the microenvironment. Microarray data of 100 ICC cases was analyzed in the EMBI database with survival data. The infiltration abundance of each epithelial cell cluster was calculated in each microarray data sample using the ssGSEA algorithm. The key epithelial cell cluster associated with poor patient outcomes was explored. The clinical value of key marker genes in this subgroup was studied. Prognostic marker genes were selected using the univariate and multivariate Cox proportional hazards(CoxPH) model. The The CoxPH model was constructed by the target genes and a nomogram was drawn. Kaplan-Meier survival analysis was used to verify the relationship between score and prognosis of patients. The predictive power of the model was evaluated by receiver operating characteristic(ROC) curves, calibration curves, and decision curve analysis (DCA). Results: Epithelial cell clusters infiltrated almost exclusively in tumor tissue. The MT2A+ epithelial cell subset was associated with a poorer prognosis for patients with a high invasion abundance and patients characterized by infiltration of this group were defined as antioxidant. After screening marker genes in this cluster using a univariate and multivariate CoxPH model, the following genes were found to be independent prognostic factors: FILPIL, NFKBIA, PEG10, SERPINB5. The CoxPH model was constructed using the four gene expression levels, and the survival rate of patients in the high-risk group was significantly lower than those in the low-risk group (all P<0.05). The constructed nomogram had good discrimination and validity. The ROC curve showed that the predicted area under the curve was 0.779, 0.844 and 0.845 at 1, 3 and 5 years, respectively. Compared to clinical indicators, the model had better predictive power using the calibration curve and the DCA test. Conclusions: The MT2A+ epithelial cell group may be associated with the prognosis of patients with ICC, and the concept of ICC tissue typing of antioxidant and non-antioxidant types is proposed. The type of antioxidant may predict the poor prognosis of the patients, and postoperative adjuvant therapy and other means could be considered to improve the survival of the patients.

[New advances in the diagnosis and treatment of intrahepatic cholangiocarcinoma].

Intrahepatic cholangiocarcinoma (ICC) is a type of primary liver cancer, which has shown an increasing trend in incidence and mortality in recent years, with a poor prognosis. The clinical diagnosis and treatment of ICC currently face the challenges of low detection rate, high mortality rate, poor treatment outcome, and urgently need more in-depth research to promote the improvement of clinical diagnosis and treatment level. In recent years, ICC diagnosis and treatment related research has made new progress in many aspects, and the knowledge about these new clinical diagnosis and treatment advances should be updated in a timely manner. This article reviewed the latest research results in recent years, summarized some new views on ICC typing, prevention and diagnosis staging that have been proposed recently, as well as the new progress made in surgical treatment and systemic treatment, and briefly discussed the potential of ICC individualized precision treatment and the occurrence of rare complications caused by combined treatment.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.