POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Glaucoma is one of the most common optic neuropathies, featuring progressive retinal ganglion cell damage and visual field loss (Tham et al., 2014; Xu et al., 2020). Currently, the only effective treatment for this condition is the reduction of intraocular pressure (IOP) (Palmberg, 2001; Heijl et al., 2002). Canaloplasty is a proven bleb-independent surgery with good efficacy and safety profiles in primary open-angle glaucoma (POAG) (Gołaszewska et al., 2021). However, early transient postoperative IOP elevation has been reported in up to 30% of cases (Riva et al., 2019), similar to that commonly observed in other internal drainage glaucoma surgeries such as implantation using iStent (0%-21.0%), CyPass (10.8%), and Hydrus (4.8%-6.5%) (Lavia et al., 2017). This complication may be a predictor of poor reserve in the outflow system and is potentially associated with surgical failure. Nonetheless, the exact pathophysiology of glaucoma remains unknown, and studies clarifying the risk factors for postoperative IOP elevation have been scarce.
Humans ; Intraocular Pressure ; Glaucoma, Open-Angle/surgery* ; Incidence ; Treatment Outcome ; Risk Factors

Objective:To establish the first Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale in China and evaluate its preliminary application value in the standardized training for radiation oncology resident physicians.Methods:Based on the educational curriculum and examination requirements for the standardized training for radiation oncology resident physicians, as well as the standardized Mini-Clinical Evaluation Exercise (Mini-CEX) scale commonly used in clinical practice, the Mini-Formative Evaluation of Radiation Oncology (Mini-FERO) scale was developed to facilitate the standardized training for resident physicians in the field of radiation oncology. In this prospective study, a randomization method using a random number table was employed to select a cohort of 26 resident physicians who completed their rotations in Department of Radiation Oncology at the Cancer Hospital, Chinese Academy of Medical Sciences from March 1, 2021 to December 31, 2021. The Mini-FERO scale was administered in the initial, middle, and final stages during the rotation period. The differences in evaluation scores before and after the assessments were analyzed by paired t-test. Furthermore, participating resident physicians and supervising teachers provided satisfaction ratings, and a comprehensive evaluation of the Mini-FERO scale was conducted. Results:The average scores of the three examinations of 26 resident physicians demonstrated a successive improvement, with individual performance in each assessed category also showing progressive enhancement. The second evaluation exhibited a more pronounced score increase compared to the first evaluation, with a mean improvement of (1.43±1.02) points ( t=7.13, P<0.001); while the third evaluation had a mean improvement of (0.41±0.50) points ( t=4.07, P<0.001) compaired to the second evaluation, with a mean difference of (1.02±1.15) points between the two ( t=4.53, P<0.001). The average time required for the assessments was (34.31±24.46) min. Overall satisfaction ratings from the evaluated resident physicians for the Mini-FERO scale were (8.42±0.85) points, and supervising teachers reported an overall satisfaction rating of (8.45±0.85) points. The satisfaction rate was 96% (25/26). Conclusions:In this study, the Mini-FERO scale was successfully developed and validated in the context of clinical teaching practice for radiation oncology resident physicians. The Mini-FERO scale is proven to be a feasible tool for assessing the gradual improvement of resident physicians throughout their learning process in the field of radiation oncology. Importantly, it offers the advantages of short assessment time, thereby avoiding additional burden on supervising teachers. The adoption of the Mini-FERO scale addresses current limitations of lacking of formative evaluation in the standardized training for radiation oncology resident physicians.

Objective:To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease.Methods:A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks.Results:Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months ( P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions:The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.

Objective To construct a nomogram prognostic model for predicting the survival of patients with lung adenocarcinoma based on the large sample data from the SEER database. Methods We retrospectively analyzed the clinical data of patients who were diagnosed with lung adenocarcinoma from 2010 to 2015 in the SEER database. A nomogram model was created based on independent parameters influencing the prognosis of patients with lung adenocarcinoma using Lasso Cox regression analysis. The C-index and calibration curve were utilized to assess the ability to distinguish and calibrate the nomogram. NRI and DCA curves were used to evaluate the prediction ability and net benefit of the nomogram. Results A total of 15 independent risk factors affecting the prognosis of lung adenocarcinoma were identified and integrated into the nomogram model. The C-index of the prediction model was 0.819 in the training cohort and 0.810 in the validation cohort. The predicted specific survival rate of the 1-, 3- and 5-year calibration curves of the training cohort and the validation cohort were consistent with the actual specific survival rate. In comparison to the 7th edition of the AJCC TNM staging system, the NRI and DCA curves demonstrated a considerable boost to the predictive capacity and net benefits achieved by the nomogram model. The risk stratification model constructed with this nomogram model was able to distinguish the patients with different risks well (P < 0.0001). Conclusion A nomogram prognostic model is successfully developed and validated, which provides a simple and reliable tool for the survival prediction of the patients with lung adenocarcinoma. Meanwhile, the risk stratification model constructed by the prediction model can conveniently screen patients with different risks, which is important for the individualized treatment of lung adenocarcinoma patients.

Objective:To systematically sort out and cluster the existing indicators of key issues in the quality of postgraduate clinical degree education based on the bibliometric study, so as to build a multidimensional quality assessment index system that integrates scientificity, rationality and representativeness, and to provide a scientific measurement tool for assessing clinical professional postgraduate education in China.Methods:By mining the related functions of UCINET6 network analysis integration software and its one-dimensional and two-dimensional data analysis NetDraw program, the social network analysis (SNA) method was used to extract and cluster the education quality problem set of clinical professional degree postgraduates.Results:A three-dimensional evaluation index system was constructed. The first dimension concluded such 8 key issues in the quality of postgraduate education in clinical medicine as ability assessment, teaching system, teaching quality assurance system, professional cognition and career prospects, assessment and evaluation system and organization, and the pulse taking and diagnosis.Conclusion:The clinical graduate education quality evaluation index system is an effective measurement tool for education quality improvement, based on a multidimensional perspective, with key issues as priority areas for intervention, providing an effective evidence-based basis for ensuring the development of professional graduate education efforts from 2020-2025.

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Objective:To understand the epidemiological characteristics of infectious diarrhea pathogens in Pudong New Areas of Shanghai from 2013 to 2017 to provide evidence for control and prevention of the disease.Methods:From Jan 2013 to Dec 2017, active surveillance program on diarrhea was conducted in 14 sentinel hospitals (three tertiary-level and nine secondary-level, and two primary-level hospitals) in Pudong New Areas of Shanghai, based on location, catchment areas and number of patients. All recruited outpatients were interviewed in hospitals, using a standard questionnaire. Stool specimens were collected and tested for five viral and eight bacterial pathogens.Results:A total of 9 301 cases with infectious diarrhea were included, and the overall positive rate was 55.7 % (5 179). Positive rates of single virus, single bacteria and mixed infections were 26.7 % (2 481), 17.0 % (1 579) and 12.0 % (1 119), respectively. For single infection, the most commonly detected viruses appeared as norovirus (15.4 %, 1 428/9 301) and rotavirus (7.2 %, 667/9 301). The most commonly detected bacteria were diarrheagenic Escherichia coli (6.7 %, 619/9 301) and non-typhoid Salmonella (3.3 %, 305/9 301). The most common mixed infections were caused by virus-bacteria (4.9 %, 459/9 301). Norovirus (17.0 %, 838/4 938) showed the highest positive rates, followed by Escherichia coli (7.2 %, 354/4 938), both seen in the age group of 20-59 years old group. Rotavirus (9.4 %, 178/1 896) and non-typhoid Salmonella (4.9 %, 93/1 896) were the most common pathogens found in the age group of 0-4 years old. The prevalence of norovirus peaked both in spring and autumn. The other peaks were seen as: Rotavirus in winter, diarrheagenic Escherichia coli in summer and non-typhoid Salmonella in summer. Conclusions:Our data showed that the positive rates of infectious diarrhea pathogens were high in Pudong New Areas of Shanghai from 2013 to 2017. The dominant pathogens would include norovirus, rotavirus and diarrheagenic Escherichia coli but with differenct distributions in age groups. Obvious seasonal patterns were also observed.