[Endometriosis-related recurrent unilateral hemorrhagic pleural effusion: a case report].

Hemorrhagic pleural effusion (PE) is common in clinical practice. According to the guidelines, the etiological diagnosis of PE should focus on the identification of common diseases. In most cases, the etiology of PE can be determined by clinical history, physical examination, laboratory and imaging examinations, and pleural biopsy or video-assisted thoracic surgery (VAST). We reported a rare case of a 32-year-old woman with recurrent unilateral hemorrhagic pleural effusion (highly correlated with menstrual cycle) and chest pain that was diagnosed as thoracic endometriosis syndrome (TES) by pathological biopsy and immunohistochemistry. Later she underwent surgery combined with hormone therapy. During the follow-up, the right PE decreased, and she had no chest pain. Therefore, women of reproductive age with regular unilateral bloody pleural effusions should be alert to TES.

Paediatric Orbital Juvenile Xanthogranuloma: A Case Series and Review of the Literature.

PURPOSE: Juvenile xanthogranuloma (JXG) is a subtype of histiocytosis characterised histologically by foamy non-Langerhan cells with Touton giant cells. It typically manifests as a single self-limiting cutaneous nodule in the paediatric population. Orbital JXG is extremely rare, and its clinical course and management are not well understood or defined. Herein we present 3 cases of orbital JXG and provide a detailed literature review. METHODS: Review of 3 cases with orbital JXG and literature review of all published cases. RESULTS: Three presented cases demonstrate the heterogeneous clinical course of orbital JXG. Although centred around the use of steroids, there is neither robust evidence nor consensus on its management. The wider JXG literature is currently concentrated around the classification of JXG with respect to histiocytosis, especially the exclusion of extracutaneous JXG as separate diseases. This separation is based on clinical, histopathological, and molecular findings. It is unclear where orbital JXG best fits in this emerging classification of JXG. CONCLUSION: Our review of the cases and literature on orbital JXG show that it may manifest with variable clinical course and its molecular pathogenic mechanism may be different to that of the cutaneous JXG.

CSMD1 regulates brain complement activity and circuit development.

Complement proteins facilitate synaptic elimination during neurodevelopmental pruning, but neural complement regulation is not well understood. CUB and Sushi Multiple Domains 1 (CSMD1) can regulate complement activity in vitro, is expressed in the brain, and is associated with increased schizophrenia risk. Beyond this, little is known about CSMD1 including whether it regulates complement activity in the brain or otherwise plays a role in neurodevelopment. We used biochemical, immunohistochemical, and proteomic techniques to examine the regional, cellular, and subcellular distribution as well as protein interactions of CSMD1 in the brain. To evaluate whether CSMD1 is involved in complement-mediated synapse elimination, we examined Csmd1-knockout mice and CSMD1-knockout human stem cell-derived neurons. We interrogated synapse and circuit development of the mouse visual thalamus, a process that involves complement pathway activity. We also quantified complement deposition on synapses in mouse visual thalamus and on cultured human neurons. Finally, we assessed uptake of synaptosomes by cultured microglia. We found that CSMD1 is present at synapses and interacts with complement proteins in the brain. Mice lacking Csmd1 displayed increased levels of complement component C3, an increased colocalization of C3 with presynaptic terminals, fewer retinogeniculate synapses, and aberrant segregation of eye-specific retinal inputs to the visual thalamus during the critical period of complement-dependent refinement of this circuit. Loss of CSMD1 in vivo enhanced synaptosome engulfment by microglia in vitro, and this effect was dependent on activity of the microglial complement receptor, CR3. Finally, human stem cell-derived neurons lacking CSMD1 were more vulnerable to complement deposition. These data suggest that CSMD1 can function as a regulator of complement-mediated synapse elimination in the brain during development.

Old World Screwworm myiasis: First report of auricular Chrysomya bezziana myiasis in a dog in Singapore.

A German Shepherd dog was presented to a referral practice for screwworm myiasis affecting the ear. The successful management involved killing the larvae with afoxolaner plus milbemycin oxime and using video otoscopy to completely remove dead larvae. To the best of our knowledge, this is the first case report of auricular myiasis by Chrysomya bezziana in a dog in Singapore and the first report of video otoscopic management of myiasis.

Protein interaction networks in the vasculature prioritize genes and pathways underlying coronary artery disease.

Population-based association studies have identified many genetic risk loci for coronary artery disease (CAD), but it is often unclear how genes within these loci are linked to CAD. Here, we perform interaction proteomics for 11 CAD-risk genes to map their protein-protein interactions (PPIs) in human vascular cells and elucidate their roles in CAD. The resulting PPI networks contain interactions that are outside of known biology in the vasculature and are enriched for genes involved in immunity-related and arterial-wall-specific mechanisms. Several PPI networks derived from smooth muscle cells are significantly enriched for genetic variants associated with CAD and related vascular phenotypes. Furthermore, the networks identify 61 genes that are found in genetic loci associated with risk of CAD, prioritizing them as the causal candidates within these loci. These findings indicate that the PPI networks we have generated are a rich resource for guiding future research into the molecular pathogenesis of CAD.

[Long-term survival analysis of 1 367 patients treated with radical nephrectomy from a single center].

Objective: To report the long-term survival of renal cell carcinoma (RCC) patients treated with radical nephrectomy in Sun Yat-sen University Cancer Center. Methods: We retrospectively analyzed the clinical, pathological and follow-up records of 1 367 non-metastatic RCC patients treated with radical nephrectomy from 1999 to 2020 in this center. The primary endpoint of this study was overall survival rate. Survival curves were estimated using the Kaplan-Meier method, and group differences were compared through Log-rank test. Univariate and multivariate Cox analysis were fit to determine the clinical and pathological features associated with overall survival rate. Results: A total of 1 367 patients treated with radical nephrectomy with complete follow-up data were included in the study. The median follow-up time was 52.6 months, and 1 100 patients survived and 267 died, with the median time to overall survival not yet reached. The 5-year and 10-year overall survival rates were 82.8% and 74.9%, respectively. The 5-year and 10-year overall survival rates of Leibovich low-risk patients were 93.3% and 88.2%, respectively; of Leibovich intermediate-risk patients were 82.2% and 72.3%, respectively; and of Leibovich high-risk patients were 50.5% and 30.2%, respectively. There were significant differences in the long-term survival among the three groups (P<0.001). The 10-year overall survival rates for patients with pT1, pT2, pT3 and pT4 RCC were 83.2%, 73.6%, 55.0% and 31.4%, respectively. There were significant differences among pT1, pT2, pT3 and pT4 patients(P<0.001). The 5-year and 10-year overall survival rates of patients with lymph node metastasis were 48.5% and 35.6%, respectively, and those of patients without lymph node metastasis were 85.1% and 77.5%, respectively. There was significant difference in the long-term survival between patients with lymph node metastasis and without lymph node metastasis. The 10-year overall survival rate was 96.2% for nuclear Grade 1, 81.6% for nuclear Grade 2, 60.5% for nuclear Grade 3, and 43.4% for nuclear Grade 4 patients. The difference was statistically significant. There was no significant difference in the long-term survival between patients with localized renal cancer (pT1-2N0M0) who underwent open surgery and minimally invasive surgery (10-year overall survival rate 80.5% vs 85.6%, P=0.160). Multivariate Cox analysis showed that age≥55 years (HR=2.11, 95% CI: 1.50-2.96, P<0.001), T stage(T3+ T4 vs T1a: HR=2.37, 95% CI: 1.26-4.46, P=0.008), local lymph node metastasis (HR=3.04, 95%CI: 1.81-5.09, P<0.001), nuclear grade (G3-G4 vs G1: HR=4.21, 95%CI: 1.51-11.75, P=0.006), tumor necrosis (HR=1.66, 95% CI: 1.17-2.37, P=0.005), sarcomatoid differentiation (HR=2.39, 95% CI: 1.31-4.35, P=0.005) and BMI≥24kg/m(2) (HR=0.56, 95%CI: 0.39-0.80, P=0.001) were independent factors affecting long-term survival after radical nephrectomy. Conclusions: The long-term survival of radical nephrectomy in patients with renal cell carcinoma is satisfactory. Advanced age, higher pathological stage and grade, tumor necrosis and sarcomatoid differentiation were the main adverse factors affecting the prognosis of patients. Higher body mass index was a protective factor for the prognosis of patients.

[Relation factor analysis for the short-term preservation of ipsilateral renal function after partial nephrectomy].

Objectives: To analyze the factors relative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Methods: The clinical data of 83 patients who were treated with partial nephrectomy from December 2014 to December 2019 in the Department of Urology, Sun Yat-sen University Cancer Center were retrospectively analyzed. There were 54 males and 29 females, aging (M (IQR)) 49 (17) years (range: 27 to 74 years). The ischemia time in operation was 25 (18) minutes (range: 10 to 67 minutes). Emission computed tomography scan and CT scan were performed before (within 1 month) and after (3 to 12 months) surgery. The volume of the ipsilateral and contralateral kidney was measured on the basis of preoperative and postoperative CT scans. The glomerular filtration rate (GFR) specifically in each kidney was estimated by emission computed tomography. Recovery from ischemia is determined by the formula: GFR preservation/volume saved×100%. Linear regression was used to explore the factors ralative to the short-term preservation of ipsilateral renal function after partial nephrectomy. Results: The GFR preservation of the ipsilateral kidney was 80.9 (25.2) % (range: 31.0% to 109.4%). The volume loss of the kidney resulted in a decrease of 12.0% (5.8 ml/(min×1.96 m2)) of GFR, while the ischemic injury resulted in a decrease of 6.5% (2.5 ml/(min×1.96 m2)) of GFR. The volume saved from the ipsilateral kidney was 87.1 (12.9) % (range: 27.0% to 131.7%). Recovery from ischemia was 93.5 (17.5) % (range:44.3% to 178.3%). In multivariate analysis, GFR preservation of the ipsilateral kidney was significantly correlated with the volume saved of the ipsilateral kidney (ß=0.383, 95%CI: 0.144 to 0.622, P=0.002). It was not related to the ischemia time (ß=0.046, 95%CI:-0.383 to 0.475, P=0.831). Conclusion: In the condition of limited ischemic time, in the short term ipsilateral renal function after partial nephrectomy is mainly determined by the loss of kidney volume, while ischemic injury only plays a minor role.

Synchronized long-read genome, methylome, epigenome, and transcriptome for resolving a Mendelian condition.

Resolving the molecular basis of a Mendelian condition (MC) remains challenging owing to the diverse mechanisms by which genetic variants cause disease. To address this, we developed a synchronized long-read genome, methylome, epigenome, and transcriptome sequencing approach, which enables accurate single-nucleotide, insertion-deletion, and structural variant calling and diploid de novo genome assembly, and permits the simultaneous elucidation of haplotype-resolved CpG methylation, chromatin accessibility, and full-length transcript information in a single long-read sequencing run. Application of this approach to an Undiagnosed Diseases Network (UDN) participant with a chromosome X;13 balanced translocation of uncertain significance revealed that this translocation disrupted the functioning of four separate genes (NBEA, PDK3, MAB21L1, and RB1) previously associated with single-gene MCs. Notably, the function of each gene was disrupted via a distinct mechanism that required integration of the four 'omes' to resolve. These included nonsense-mediated decay, fusion transcript formation, enhancer adoption, transcriptional readthrough silencing, and inappropriate X chromosome inactivation of autosomal genes. Overall, this highlights the utility of synchronized long-read multi-omic profiling for mechanistically resolving complex phenotypes.

Experimental capabilities for liquid jet samples at sub-MHz rates at the FXE Instrument at European XFEL.

The Femtosecond X-ray Experiments (FXE) instrument at the European X-ray Free-Electron Laser (EuXFEL) provides an optimized platform for investigations of ultrafast physical, chemical and biological processes. It operates in the energy range 4.7-20 keV accommodating flexible and versatile environments for a wide range of samples using diverse ultrafast X-ray spectroscopic, scattering and diffraction techniques. FXE is particularly suitable for experiments taking advantage of the sub-MHz repetition rates provided by the EuXFEL. In this paper a dedicated setup for studies on ultrafast biological and chemical dynamics in solution phase at sub-MHz rates at FXE is presented. Particular emphasis on the different liquid jet sample delivery options and their performance is given. Our portfolio of high-speed jets compatible with sub-MHz experiments includes cylindrical jets, gas dynamic virtual nozzles and flat jets. The capability to perform multi-color X-ray emission spectroscopy (XES) experiments is illustrated by a set of measurements using the dispersive X-ray spectrometer in von Hamos geometry. Static XES data collected using a multi-crystal scanning Johann-type spectrometer are also presented. A few examples of experimental results on ultrafast time-resolved X-ray emission spectroscopy and wide-angle X-ray scattering at sub-MHz pulse repetition rates are given.

Comparison of Community Pharmacist and Non-Community Pharmacist Perceptions of a Community Pharmacy Specialty Board Certification.

Background: Pharmacy board certification provides pharmacists with formal recognition of their careers and their involvement in direct and comprehensive patient care. Credentialing as a board-certified pharmacist demonstrates that the pharmacist has specialized expertise and is able to provide advanced level patient care in a specific pharmacy practice specialty. There is currently not a community pharmacy board certification available in the United States. With the expanding role and clinical expectations of community pharmacists nationwide, perspectives regarding the utility of a community pharmacy specialty board certification are necessary. Methods: A cross-sectional survey with demographic and perception questions (5-point Likert scale) was distributed electronically via Qualtrics. A random sample of pharmacists registered in Rhode Island, Ohio, and Nebraska were selected and surveyed. Results: 53 survey responses were collected. There was a statistically significant difference in board certification history (P = .001) and history of post-graduate training (P < .001) between community pharmacists and non-community pharmacists. Community pharmacists were more likely to simultaneously see community pharmacists as general practitioners (P = .030) and as pharmacy practice specialists (P = .001). Non-community pharmacists were more likely to be familiar with current maintenance requirements for pharmacy board certifications (P < .001) and to feel that a board certification is an appropriate indicator of experience in a pharmacy specialty area (P = .016). Conclusion: Views regarding community pharmacy and board certification differed between community and non-community pharmacists. There was not a statistically significant difference in the perceived value of community pharmacy board certification between community and non-community pharmacist.

[The comparison between endoscopic and surgical treatment of delayed iatrogenic bile duct injury by propensity score matching].

Objective: To compare the safety and clinical efficacy of endoscopic and surgical treatment of patients with delayed iatrogenic bile duct injury (DBDI) with severity (SG) grade 1 to 2. Methods: The clinical data of 129 patients with SG grade 1 to 2 DBDI who received endoscopic or surgical treatment in the First Hospital of Lanzhou University from November 2007 to November 2021 were retrospectively collected. There were 46 males and 83 females,aged (M(IQR)) 54(22)years(range: 21 to 82 years). The baseline data of the two groups were matched 1∶1 by propensity score matching(caliper value was 0.2). Independent sample t test,rank sum test,χ2 test or Fisher exact probability test were used to analyze the data of the two matched groups. Results: There were 48 patients in each of the endoscopic treatment and surgical groups after matching,and there was no difference in general information between the two groups(both P>0.05). The bile duct injury-repair interval and intraoperative anesthesia complications were not statistically significant between the two groups after matching(all P>0.05). Compared with the surgical group, patients in the endoscopic treatment group had significantly shorter operative time(50 (30) minutes vs. 185 (100) minutes, Z=7.675,P<0.01) and postoperative hospital stay(5 (5) days vs. 12 (7) days, Z=5.848, P<0.01).For safety,there was no statistical difference in the incidence of immediate postoperative complications between the two groups with Clavien-Dindo classification of surgical complications<Ⅲ;the incidence of serious postoperative complications (Clavien-Dindo classification of surgical complications≥Ⅲ) was significantly higher in the surgical group than in the endoscopic treatment group(P=0.012). The incidence of long-term postoperative complications was not statistically different between the two groups(28.1% vs. 20.7%,P=0.562). In terms of efficacy,the postoperative liver function indexes of patients in both groups improved significantly compared with the preoperative period and returned to normal or near normal levels; the postoperative infection indexes of both groups showed an increasing trend,but were within the normal range. Of the 96 patients in both groups,61 obtained follow-up,and the follow-up time was (89.4±48.0)months(range: 3 to 165 months),and there was no statistical difference between the two groups(P=0.079). The probability of excellent long-term follow-up (78.1% vs. 86.2%) was not statistically different between the two groups(P=0.412).In patients with Strasberg-Bismuth type E1,the probability of excellent long-term follow-up was higher in the endoscopic treatment group compared with the surgical group(13/14 vs. 2/5,P=0.037). Conclusions: For DBDI patients with SG grade 1 to 2 and bile duct continuity,endoscopy can be used as the first deterministic treatment. The advantages of endoscopic therapy compared to surgery are the lower incidence of postoperative serious complications,and the shorter duration of surgery and postoperative hospital stay.

Impact of carbapenem-targeted antimicrobial stewardship interventions: an interrupted time-series analysis.

BACKGROUND: The development of carbapenem-resistant Gram-negative bacilli (CR-GNB) is largely favoured by indiscriminate and prolonged carbapenem use, which is a significant contributing factor. AIM: To evaluate the impact of two carbapenem antibiotic stewardship programme interventions on both carbapenem prescriptions and the clinical isolation rates of CR-GNBs, using interrupted time-series analysis. METHODS: A time-series analysis was performed using data for carbapenem usage from a tertiary hospital in South Korea from January 2017 to July 2022. Two carbapenem antibiotic stewardship programme interventions were implemented sequentially: (i) a prospective audit and feedback (PAF) from November 2018 to April 2020 (intervention 1), and (ii) preauthorization from May 2020 to August 2020 (intervention 2). Monthly carbapenem usage and incidence of CR-GNB before and after each intervention were compared using an autoregressive integrated moving average model. FINDINGS: Implementation of PAF resulted in a significant reduction in carbapenem consumption, followed by an additional decrease after the preauthorization was implemented. The incidence of carbapenem-resistant Escherichia coli and Klebsiella pneumoniae increased after intervention 1, but there was a significant change from an increasing trend to a stationary trend after intervention 2. The incidence of carbapenem-resistant Pseudomonas aeruginosa, which had increased during the baseline period, became stationary after intervention 1. A significant decrease was observed in the incidence of carbapenem-resistant Acinetobacter baumannii during the implementation of intervention 1 and 2. CONCLUSION: This study emphasizes the importance of adopting comprehensive antibiotic management and rigorous infection control to prevent infections caused by antibiotic-resistant bacteria.

[Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy].

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

[Efficacy and safety evaluation of immunotherapy combined with targeted therapy as second-line treatment in patients with metastatic non-clear cell renal cell carcinoma].

Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.

Becoming a resilient scientist series: An intervention program.

Compared to the general population, science trainees experience challenges and heightened stressors that often lead to adverse mental health outcomes. With COVID-19, the stressors of social distancing, isolation, truncated lab time, and uncertainty about the future have all likely exacerbated these issues. Now, more than ever, practical and effective interventions are vitally needed to address the core causes of stress among science trainees and increase their resilience. This paper introduces a new resilience program targeted to biomedical trainees and scientists - Becoming a Resilient Scientist Series (BRS), a multi-part workshop complemented by facilitated group discussions all aimed at bolstering resilience, particularly in the context of academic and research environments. To assess the program's efficacy, participants completed resilience measures and related assessments before and after completing the series. The results demonstrate that BRS significantly enhances trainee resilience (primary outcome) and reduces perceived stress, anxiety, and work-related presenteeism, as well as increased adaptability, self-awareness, and self-efficacy (secondary outcomes). Furthermore, program participants reported a high level of satisfaction, a strong willingness to recommend the program to others, and perceived positive changes in their resilience skills. To the best of our knowledge, this is the first resilience program designed explicitly for biomedical trainees and scientists, tailored to their unique professional culture and work environment.

Molecular cloning, expression analysis and functional characterization of chicken cytochrome P450 27A1: A novel mitochondrial vitamin D3 25-hydroxylase.

Vitamin D3 is hydroxylated by cytochrome P450 (CYP) before exerting biological effects. The chicken CYP involved in vitamin D3 25-hydroxylation has yet to be cloned, and little is known about its functional characteristics, tissue distribution, and cellular expression. We identified a novel, full-length CYP27A1 gene cloned from chicken hepatocyte cDNA that encodes a putative protein of 518 amino acids. Swiss modeling revealed that chicken CYP27A1 has a classic open-fold form. Multisequence homology alignment determined that CYP27A1 contains conserved motifs for substrate recognition and binding. Quantitative real-time PCR analysis in 2-mo-old Partridge Shank broilers demonstrated that CYP27A1 mRNA levels were highest in the liver, followed by the thigh muscles, the breast muscles, and kidneys. The transcripts of CYP27A1 in breast muscles were significantly higher in males than in females. A subcellular localization analysis demonstrated that CYP27A1 was mainly expressed in the mitochondria. In vitro enzyme assays suggested that recombinant CYP27A1 hydroxylates vitamin D3 at the C-25 position to form 25-hydroxyvitamin D3 (25(OH)D3). The Km and Vmax values for CYP27A1-dependent vitamin D3 25-hydroxylation were estimated to be 4.929 µM and 0.389 mol min-1 mg-1 protein, respectively. In summary, these results suggest that CYP27A1 encodes a mitochondrial CYP that plays an important physiologic role in the 25-hydroxylation of vitamin D3 in chickens, providing novel insights into vitamin D3 metabolism in this species.

[Clinical efficacy and safety analysis of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer].

Objective: To investigate the clinical efficacy and safety of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer. Methods: Clinical data of 36 patients who underwent CT-guided 125I seed implantation for mediastinal lymph node metastasis of lung cancer from August 2013 to April 2020 in three hospitals of the Northern radioactive particle implantation treatment collaboration group were retrospectively collected, including 24 males and 12 females, aged 46 to 84 years. Cox regression model was used to analyze the relationship between local control rate, survival rate and tumor stage, pathological type, postoperative D90, postoperative D100 and other variables, and to analyze the occurrence of complications. Results: The objective response rate of CT-guided 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer was 75% (27/36), the median control time was 12 months, the 1-year local control rate was 47.2% (17/36), and the median survival time was 17 months. The 1-year and 2-year survival rates were 61.1% (22/36) and 22.2% (8/36) respectively. Univariate analysis showed that in the treatment of mediastinal lymph node metastasis with CT-guided 125I implantation, factors related to local control included tumor stage (HR=5.246, 95%CI: 2.243-12.268, P<0.001), postoperative D90 (HR=0.191, 95%CI: 0.085-0.431, P<0.001), postoperative D100 (HR=0.240, 95%CI: 0.108-0.533, P<0.001); The factors affecting survival were tumor stage (HR=2.712, 95%CI: 1.356-5.425, P=0.005), postoperative D90 (HR=0.110, 95%CI: 0.041-0.294, P<0.001), postoperative D100 (HR=0.212, 95%CI: 0.092-0.489, P<0.001). Multivariate analysis showed that tumor stage (HR=5.305, 95%CI: 2.187-12.872, P<0.001) and postoperative D100 (HR=0.237, 95%CI: 0.099-0.568, P<0.001) were correlated with local control rate. Tumor stage (HR=2.347, 95%CI: 1.095-5.032, P=0.028) and postoperative D90 (HR=0.144, 95%CI: 0.051-0.410, P<0.001) were correlated with survival. In terms of complications, 9 of the 36 patients had pneumothorax, and 1 of them was cured by closed thoracic drainage for severe pneumothorax; 5 cases developed pulmonary hemorrhage and 5 cases developed hemoptysis, which recovered after hemostasis treatment. One case developed pulmonary infection and recovered after anti-inflammatory treatment. No radiation esophagitis and radiation pneumonia occurred; No grade 3 or higher complications occurred. Conclusion: 125I seed implantation in the treatment of lung cancer mediastinal lymph node metastasis has a high local control rate and controllable adverse effects.

Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia.

Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

[Research progress on signaling pathways related to drug research in proliferative vitreoretinopathy].

Proliferative vitreoretinopathy (PVR) is an avascular fibroproliferative disease that occurs in the retina. The main pathological changes are the proliferation and traction of retinal pigment epithelial cells (RPE) and glial cells on the vitreous and retina. Basic research has confirmed that the formation of PVR is related to multiple signaling pathways, including NK-κB signaling pathway, MAPK and its downstream signaling pathways, JAK/STAT signaling pathway, PI3K/Akt signaling pathway, thrombin and its receptor pathway, TGF-ß and downstream signaling pathway, North signaling pathway and Wnt/ß-catenin signaling pathway, etc. This review summarizes the research progress of the main signaling pathways in the formation mechanism of PVR, and provides the basis and support for the research of PVR drug therapy.