AIM: To investigate the application of biological amniotic membrane soaked in pirfenidone(PFD)and to evaluate its anti-scarring effect and toxic side effects on glaucoma model of rabbit eyes.METHODS: The right eyes of 72 healthy New Zealand white rabbits were randomly divided into 0.5%PFD+ biological amniotic membrane group, biological amniotic membrane group, mitomycin C(MMC)group and blank control group after the glaucoma model was established by anterior chamber injection of compound carbomer solution, and 18 rabbits in each group underwent trabeculectomy, in which the 0.5% PFD+ biological amniotic membrane group was placed with 0.5% PFD solution-soaked biological amniotic membrane under the scleral flap, and the biological amniotic membrane group was placed with normal saline-soaked rehydrated biological amniotic membrane under the scleral flap. In the MMC group, a cotton pad soaked in MMC was placed under the scleral flap for 3 min and immediately rinsed with normal saline, while the blank control group received no implant after the scleral flap was made. The intraocular pressure(IOP), filtration blebs, toxic side effects and complications were evaluated, and the histopathological changes in the filtration area were observed by hematoxylin-eosin(HE), Masson staining and immunohistochemical staining.RESULTS: The mean IOP at 14, 21 and 28 d after trabeculectomy were 0.5%PFD+ biological amniotic membrane group<MMC group<biological amniotic membrane group<blank control group(all P<0.05). At 28 d after trabeculectomy, 0.5%PFD+ biological amniotic membrane group had the best effect of anti-inflammatory hyperplasia and inhibition of collagen formation, the highest survival rate of filtration blebs, and the inflammatory reaction was mild.CONCLUSION: Biological amniotic membrane soaked in pirfenidone has more obvious anti-scarring effect on glaucoma model, with less toxic side effects and good safety.

Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L⁻¹). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L⁻¹), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L⁻¹ after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L⁻¹, respectively (P<0.05). After exposure to 30 mmol·L⁻¹ and 100 mmol·L⁻¹ DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L⁻¹ DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L⁻¹ group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L⁻¹ DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L⁻¹ and 100 mmol·L⁻¹ can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.

Objective The aim of this study is to analyze the current situation and influencing factors of specialist nurses'work in 72 tertiary hospitals in Anhui Province which can provide suggestions for the training and use of specialist nurses.Methods Using stratified sampling,a survey of 2,400 specialist nurses in 72 tertiary hospitals across the province were recruited and investigated by a self-administered questionnaire on the current work status and competencies of specialist nurses,from December 2022 to January 2023.The one-way ANOVA and multiple linear regression methods to analyze the influencing factors.Results A total of 2,248 valid questionnaires were returned from specialist nurses,with a validity rate of 93.67%.Specialist nurses scored(19.07±5.11)for their current work status and(17.07±2.84)for their ability to work.The results of multiple linear regression analyses showed that the level and nature of the hospital,title,position,method of obtaining training qualifications,working time in the speciality after training,and the competence of the specialist nurses were the factors influencing the current status of the specialist nurses'work(P<0.05).Conclusion The current status of specialist nurses'work in tertiary hospitals in Anhui Province is relatively satisfactory,and it is influenced by the level and nature of the hospital,the way of training and selection,and factors of the specialist nurses themselves.It is recommended to pay attention to the subsequent use and training of specialist nurses to improve their ability to work and provide high-quality professional care to patients.

Objective To investigate the effects of long-term exposure to three new types of light emitting diode (LED) sources on the behavior, learning, and memory of rats. Methods A total of 160 specific pathogen-free SD rats were divided into eight groups as followed, trichromatic fluorescent lamps color temperature control group, violet-chip full-spectrum white LED group, blue-chip white LED group, and blue-chip full-spectrum white LED group based on the light sources types, with color temperature of 4 000 K and 6 500 K groups in each group using the 4×2 factorial design. There were 20 rats in each group, with half of the rats were males and half females. Rats were exposed to artificial lighting, and the illumination was set at 750 lx. The rats in each group were exposed to different lighting environments for 12 hours per day for 24 weeks. The open-field and step-down tests were conducted in rats after 24 weeks exposure, followed by sacrifice of rats and measurement of organ coefficients. Differences in body weight, organ coefficients, and neurobehavioral indexes of rats in different groups were compared. Results The spleen coefficient of female rats decreased in blue-chip white LED of 6 500 K color temperature group, and the liver coefficient of male rats decreased in the violet-chip full-spectrum white LED of 4 000 K color temperature, blue-chip full-spectrum white LED of 4 000 K color temperature, and blue-chip full-spectrum white LED of 6 500 K color temperature groups, compared with the same-sex rats in trichromatic fluorescent lamps with same-color temperature control group (all P<0.05). The result of different types of light sources compared in the open-field test showed that the index of total distance and movement speed of female rats in the blue-chip full-spectrum white LED group were lower than those in the other three groups, and the time cost to the central area was longer than that in the blue-chip white LED group and the violet-chip full-spectrum white LED group (all P<0.05). The total distance and movement speed of male rats in the blue-chip full-spectrum white LED group were longer or higher than those in the violet-chip full-spectrum white LED group (all P<0.05). Based on the comparison of color temperature, the time and total distance of male rats in 6 500 K color temperature group were lower than that in the 4 000 K color temperature group (both P<0.05). In the step-down test, both male and female rats in the blue-chip full-spectrum white LED group made more errors compared with other three groups with the same gender (all P<0.05). Conclusion Based on the experimental conditions of this study, the blue-chip full-spectrum white light LED affects behavior, learning and memory of the rats, and trichromatic fluorescent lamp has the lowest effect on neurobehavior. The color temperature also affects behavior of the rats, and high color temperature has higher risk.

OBJECTIVE: To summarize the clinical features and spectrum of genetic variants in 12 patients with Loeys-Dietz syndrome (LDS), and to explore the correlation between the type of genetic variants and clinical phenotypes. METHODS: Twelve patients suspected for LDS at Beijing Anzhen Hospital Affiliated to Capital Medical University from January 2015 to January 2022 were selected as the study subjects. Clinical data of the patients were collected. Genomic DNA was extracted from peripheral blood samples and subjected to genetic testing. Pathogenicity of candidate variants was analyzed. RESULTS: The clinical phenotypes of the 12 patients have mainly included cardiovascular, musculoskeletal, craniofacial, skin, ocular and other systemic signs. Four patients (patients 5-1, 5-2, 6, 7) have carried heterozygous missense variants of the TGFBR1 gene, 5 patients (patients 1-1, 1-2, 2, 3, 4) have carried heterozygous variants of the TGFBR2 gene, and 2 patients (patients 8-1, 8-2) had carried heterozygous frameshift variants of the TGFB3 gene. One patient (patient 9) had carried a heterozygous missense variant of the SMAD3 gene. Among these, TGFBR1 c.603T>G (p.1201M) and TGFB3 c.536delA (p.H179FS35) had not been reported previously. CONCLUSION Variants of the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 and SMAD2 genes are mainly associated with LDS. The severity of the disease phenotype caused by the same variant may vary, whilst the clinical phenotype caused by different variant sites may be specific.
Humans ; Loeys-Dietz Syndrome/genetics* ; Receptor, Transforming Growth Factor-beta Type I/genetics* ; Receptor, Transforming Growth Factor-beta Type II/genetics* ; Transforming Growth Factor beta3 ; Face

Humans ; Multiple Pulmonary Nodules ; Lung ; Lung Neoplasms/surgery* ; Solitary Pulmonary Nodule/surgery* ; Bronchoscopy

Objective     To analyze the echocardiographic characteristics of above grade 3+ mitral regurgitation (MR) patients by 3D transesophageal echocardiography (3D-TEE) in transcatheter edge-to-edge repair (TEER) and compare the intervention rate of TEER treatment in patients with different risk stratification. Methods     We retrospectively analyzed the clinical data of 91 patients with above grade 3+ MR in Anzhen Hospital between June 2021 and April 2022. There were 45 males and 46 females aged 66.5±15.9 years. According to pathogenesis, the patients were divided into different anatomical groups and risk stratification groups. There were 34 patients in a simple degenerative group (simple DMR group), 28 patietns in a complex disease group (Complex group), 14 patients in a simple ventricular  functional reflux group (simple VFMR group), 9 patients in a simple atrial functional reflux group (simple AFMR group), and 6 patients in a mixed functional reflux group (mixed FMR group). All patients were examined with a unified standard of transthoracic echocardiography (TTE) and 3D-TEE to compare the characteristic three-dimensional structural changes of the mitral valve in each group. According to the three partition strategy of preoperative anatomical evaluation of TEER, the risk stratification was conducted for the enrolled patients, which was divided into three regions from light to heavy: green area, yellow area, and red area. TEER treatment intervention rate of patients with different risk stratification was calculated. Results     Ant leaf angle and post leaf angle were negative in the simple DMR and Complex groups, and non-planar angle, prolapse height and prolapse volume were higher than those of the other groups (P=0.000). Ant leaf angle and post leaf angle were positive in the VFMR group and the mixed FMR group. Anterior and posterior (AP) diameter of valve ring (P=0.036), tenting height and tenting volume were higher than those of other groups (P=0.000).  AP diameter, tenting height and tenting volume were changed mildly in patients with simple AFMR. MR patients in red and yellow zone achieved a 28.1% TEER intervention rate. Conclusion     Standardized TTE and TEE examinations are crucial for the qualitative and quantitative diagnosis of MR in the echo core-lab. 3D-TEE mitral valve parameter can help determine the exact pathogenesis of MR and to improve the interventional rate of challenging MR patients.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

l-Heptopyranoses are important components of bacterial polysaccharides and biological active secondary metabolites like septacidin (SEP), which represents a group of nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. However, little is known about the formation mechanisms of those l-heptose moieties. In this study, we deciphered the biosynthetic pathway of the l,l-gluco-heptosamine moiety in SEPs by functional characterizing four genes and proposed that SepI initiates the process by oxidizing the 4'-hydroxyl of l-glycero-α-d-manno-heptose moiety of SEP-328 ( 2) to a keto group. Subsequently, SepJ (C5 epimerase) and SepA (C3 epimerase) shape the 4'-keto-l-heptopyranose moiety by sequential epimerization reactions. At the last step, an aminotransferase SepG installs the 4'-amino group of the l,l-gluco-heptosamine moiety to generate SEP-327 ( 3). An interesting phenomenon is that the SEP intermediates with 4'-keto-l-heptopyranose moieties exist as special bicyclic sugars with hemiacetal-hemiketal structures. Notably, l-pyranose is usually converted from d-pyranose by bifunctional C3/C5 epimerase. SepA is an unprecedented monofunctional l-pyranose C3 epimerase. Further in silico and experimental studies revealed that it represents an overlooked metal dependent-sugar epimerase family bearing vicinal oxygen chelate (VOC) architecture.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95％ confidence interval (CI), 1.01?1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95％ CI, 1.49?2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95％ CI, 0.48?1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95％ CI, 0.39?1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A (USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95％ CI, 0.32?0.82; P=0.0077), PFS (adjusted HR, 0.51; 95％ CI, 0.38?0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95％ CI, 2.75?8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95％ CI, 1.88?6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12C mutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.