Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women.Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development.Stress leads to dysfunctions of cells,molecules and neural circuits,thus promoting depression.Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients.

Objective: To systematically evaluate the factors affecting diabetic retinopathy (DR) among Chinese adult patients with type 2 diabetes mellitus (T2DM), so as to provide insights into establishment of personalized risk prediction models for DR. Methods: Case-control studies pertaining to factors affecting DR among Chinese adults were retrieved from international and national databases, including CNKI, Wanfang Data, SinoMed, PubMed, Web of Science, Embase and CINAHL from inception to March 31, 2023. A meta-analysis was performed using the software Stata 17.0, and subgroup analysis was performed to explore the source of heterogeneity. Sensitivity analysis was performed using the leave-one-out method, and the publication bias was evaluated using the Egger's test and trim-and-fill method. Results: Totally 4 969 publications were retrieved, and 35 case-control studies were finally enrolled, including 32 high-quality publications (91.43%). The included studies involved 29 228 participants and 10 568 DR patients, and the prevalence of DR was 36.16%. Meta-analysis revealed that age (OR=1.06, 95%CI: 1.00-1.13), duration of T2DM (OR=1.09, 95%CI: 1.08-1.11), systolic blood pressure (OR=1.02, 95%CI: 1.01-1.03), glycated hemoglobin A1c (OR=1.38, 95%CI: 1.26-1.50), fasting blood glucose (OR=1.57, 95%CI: 1.07-2.31), urinary albumin to creatinine ratio (OR=1.50, 95%CI: 1.10-2.04), serum uric acid (OR=1.01, 95%CI: 1.00-1.01), urine microprotein (OR=2.01, 95%CI: 1.96-2.07), triglyceride (OR=1.77, 95%CI: 1.42-2.21), and total cholesterol (OR=1.82, 95%CI: 1.50-2.21) were risk factors for DR, and glomerular filtration rate (OR=0.98, 95%CI: 0.97-0.98) and C-peptide (OR=0.79, 95%CI: 0.68-0.93) were protective factors for DR. Sensitivity analysis of age effects was not robust. Following adjustment for glomerular filtration rate with the trim-and-fill method, there was still a publication bias, and the publication bias of other influencing factors had no impact on pooled effects. Conclusions Age, course of T2DM, systolic blood pressure, glycated hemoglobin A1c, fasting blood glucose, urinary albumin to creatinine ratio, serum uric acid, urine microprotein, triglyceride and total cholesterol were risk factors, and glomerular filtration rate and C-peptide were protective factors for DR among Chinese adults.

Background: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods: β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

Objective:To analyze common respiratory pathogens epidemiology in hospitalized children with lower respiratory tract infection (LRTI) in a single center in Shanghai, and to provide the basic data support for clinical diagnosis and treatment of children with LRTI in Shanghai.Methods:Children with LRTI in Children′s Hospital of Fudan University were enrolled from January 1, 2015 to December 31, 2019, and respiratory samples were collected and tested by direct immunofluorescence assay and real time polymerase chain reaction. The epidemiological characteristics of different respiratory pathogens were analyzed. Chi-square test was used for statistical analysis.Results:A total of 18 716 children were included, the total detection rate of respiratory pathogens was 36.96% (6 918/18 716), and the most frequent detected pathogen was Mycoplasma pneumoniae (MP) (15.31%(2 866/18 716)), followed by respiratory syncytial virus (RSV) (10.40%(1 946/18 716)) and parainfluenza virus Ⅲ (PIV-Ⅲ) (4.65%(871/18 716)). The detection rate of pathogens in female was significantly higher than that in male (38.48%(2 936/7 630) vs 35.92%(3 982/11 086), χ2=12.72, P<0.001). RSV and influenza virus A (Flu-A) infections peaked in winter. The detection rates of influenza virus B (Flu-B) and human metapneumovirus (MPV) were higher in winter and spring. PIV-Ⅲ infection peaked in spring and summer. The peak of PIV-Ⅱ infection occurred in summer and autumn. The infections of adenovirus (ADV), MP, Chlamydia trachomatis (CT) and PIV-Ⅰ were prevalent throughout the year without significant seasonality. The detection rate of RSV declined with age, while the detection rate of MP increased with age. The co-infection rate was 1.65%(309/18 716), and the predominant co-infection type was MP and RSV (0.37%(70/18 716)). Conclusions:A variety of pathogens lead to children′s LRTI in Shanghai from 2015 to 2019, with the common infection of MP, RSV and PIV-Ⅲ. Different pathogens showed different epidemiological characteristics in age and season distributions.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Objective:To investigate the epidemiological characteristics of classic human astrovirus (HAstV) among children under five years old with acute diarrhea, and to understand the role of HAstV in children acute diarrhea.Methods:A total of 1 010 fecal specimens were collected in 1 010 outpatients under five years old with acute diarrhea admitted to Children′s Hospital of Fudan University, Shanghai from January 2012 to December 2016. Reverse transcription polymerase chain reaction (PCR) or PCR was used for screening classic HAstV, group A rotavirus, norovirus and adenovirus. Genotypes of classic HAstV were determined by nucleotide sequencing and phylogenetic tree analysis.Results:The overall positive rate of classic HAstV was 2.7%(27/1 010). The detection rates of classic HAstV from 2012 to 2016 were 6.9%(10/144), 3.5%(5/144), 2.1%(3/144), 1.5%(4/265) and 1.6%(5/313), respectively. Almost 96.3%(26/27) of children infected with HAstV were 0 to 36 months of age. The prevalence of classic HAstV infections displayed a typical autumn/winter seasonality except in 2016. All the positive classic HAstV strains were genotyped as HAstV-1 with two lineages of HAstV-1a and HAstV-1b. Among them, the lineage of HAstV-1a was the predominant subtype (63.0%, 17/27). There were 77.8%(21/27) of the children with acute diarrhea only infected with classic HAstV, whereas for the remaining cases a variety of other enteric viruses were detected (three cases co-infected with HAstV and group A rotavirus, two cases co-infected with HAstV and adenovirus, and one case co-infected with HAstV, group A rotavirus and adenovirus).Conclusions:Children infected with HAstV are mainly less than 36 months of age. Although the genotype of classic HAstV detected in this study is single, but the lineages are in a state of dynamic change. Long-time and continuous monitor for the epidemiology of classic HAstV is needed to avoid outbreak of diarrhea in children.

Objective To evaluate the clinical efficacy and toxicity of concurrent pemetrexed-cisplatin (PP) or docetaxel-cisplatin (DP) with intensity-modulated radiation therapy (IMRT) in patients with stageⅠV lung adenocarcinoma. Methods Stage IV lung adenocarcinoma patients with unknown EGFR mutation status or wild-type admitted to Guizhou Cancer Hospital from 2011 to 2016 were randomly assigned into the PP (n=50) and DP groups (n=51).All patients received concurrent IMRT of the chest at a prescription dose of 60-70 Gy. Primary endpoint was 1-year survival rate, and secondary endpoint was acute toxicity. Results The overall response rate was 68. 0％ and 72. 5％ in the PP and DP groups (χ2=0. 250, P=0. 617) . The median survival time was 19. 6 months ( 95％CI 13. 9-25. 3) versus 12. 1 months ( 95％CI 10. 7-13. 5) in the PP and DP groups. The 1-, 2-and 3-year overall survival rates were 72. 0％ versus 52. 9％, 28. 0％ versus 17. 6％, and 16. 0％ versus 13. 7％, respectively in the PP and DP groups ( P=0. 049) . In the PP and DP groups, the incidence of grade 3-4 leukopenia was declined by 48％ and 63％( P=0. 098) , and the incidence of grade 3-4 neutropenia was decreased by 34％ and 65％( P=0. 002) , the incidence of grade 3-4 anemia was reduced by 38％ and 10％(P=0. 024), and the incidence of grade 3-4 thrombocytopenia was declined by 40％ and 14％( P=0. 003) . The incidence rate of grade 2 pneumonitis ( P=0. 625) and grade 3 esophagitis ( P=0. 484) were similar in both groups. No patients experienced ≥grade 3 pneumonitis or ≥ grade 4 radiation esophagitis. Conclusions Pemetrexed-cisplatin combined with chemoradiotherapy yields higher clinical efficacy compared with docetaxel-cisplatin plus concurrent chemoradiation in the treatment of stageⅠV lung adenocarcinoma. The incidence of radiation pneumonitis and esophagitis is similar. The incidence and severity of hematological toxicity does not significantly differ between two groups.Treatment-related toxicity is tolerable in both groups. Clinical Trial Registration Chinese Clinical Trial Registry ( ChiCTR-TRC-13004184) .

Objective To observe the therapeutic effect of the Valpar system combined with computer-aided technology in treating early vascular cognitive impairment (VCI).Methods Forty patients in the early stage of VCI were randomly divided into a treatment group and a control group,each of 20.Regular and computer-aided cognition training were applied in both groups,while training using the Valpar system was additionally used in the treatment group.Patients in both groups were assessed using the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) and the modified Barthel Index (MBI) before,and after 4 and 8 weeks of treatment.Results Before the treatment,there were no significant differences between the 2 groups in LOTCA and MBI scores (P＞0.05).After 4 and 8 weeks of treatment,the average total LOTCA score in the observation group was significantly better than before the treatment,as were the average scores on the various dimensions,and the average MBI score (P＜0.05).After 4 weeks of treatment the control group showed significant improvement in the patients' orientation (3.50±0.89),visual perception (13.50± 1.43),spatial perception (2.40±0.50),visuomotor construction (24.00± 1.17) and attention (2.30±0.87).However,after both 4 and 8 weeks of treatment,all the measurements of the observation group were significantly better than those of the control group at the same time point (P＜0.05).Conclusion The Valpar system can significantly improve the recovery of cognitive function and ability in the activities of daily living of patients in the early stage of VCI.It is worth applying in clinical practice.

Objective To compare the molecular epidemic characteristics of human astrovirus (HAstV) between outpatient and hospitalized children with acute diarrhea,and to investigate the relationship between HAstY infection and diarrhea in children.Methods A total of 298 cases were randomly collected from hospitalized children from January 2008 to December 2010 in Children's Hospital of Fudan University,and 360 specimens were collected from outpatients with acute diarrhea from August 2010 to July 2011.Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect rotavirus (RV),human calicivirus (HuCV),HAstV and human adenovirus (HAdV).H AstV genotype was determined by gene sequencing and phylogenetic analysis.Results Epidemiology of HAstV in hospitalized children was as follows:among the included 298 samples,HAstV was detected in 27.2％ (81/298) of the patients,compared with 33.9％ (42/124),33.8％ (25/74) and 14.0％ (14/100),respectively from 2008 to 2010.HAstV diarrhea occurred throughout the year and peaked in January,March,and April.95.1％ (77/81) of the infected children were 0-35 months old.All the episodes of HAstV were mixed with other diarrhea virus infection.Molecular epidemiology of HAstV in outpatient children with diarrhea was as follows:the overall incidence of HAstV was 1.9 ％ among the 360 cases (7/360).The seasonal distribution of HAstV's gastroenteritis showed a peak in November.All the outpatient children were 0-35 months old.Three cases were single infection with HAstV and the others were coinfection with RV (3 cases) or HAdV (1 case).All of the detected HAstV,either in inpatients or outpatients,belonged to HAstV-1.Conclusions The detection rate of HAstV in hospitalized children is significantly higher than that in outpatients.Most HAstV infections in hospitalized children are ascribed to nosocomial infections.Most episodes of HAstV infection were accompanied with other diarrhea viruses infection.HAstY single infection is seen in outpatient children while the detection rate is very low,implying that HAstV co-infection with other viruses plays a main role in diarrhea in most instances.

OBJECTIVETo photoelastically investigate the difference in load distribution of Tension More (TM) implants with different conical angle designs.

METHODSThe following five groups of implants of different conical angles were designed: cylinder implant, upper 1/3 TM implant (taper length of 3 mm); 1/2 TM implant (taper length of 5 mm); lower 1/3 TM implant (taper length of 7 mm); and bottom TM implant (taper length of 10 mm). The implants were centrally located in individually photoelastic models consisting of a simulated trabecular bone and a 1 mm-thick layer of cortical bone. Vertical and 45° oblique static loads were applied at the center of the superstructures. The resulting stresses were monitored photoelastically and recorded photographically. RESULTS With vertical loading, the cylinder implant showed higher stress levels in the cortical bone and trabecular bone than the upper 1/3 TM implant, 1/2 TM implant, and lower 1/3 TM implant. The four groups of TM implants showed lower stress levels in the cortical bone than the cylinder implant under oblique loads. The least favorable stress concentration in cortical bone was observed in the upper 1/3 TM implant under vertical and oblique loads.

CONCLUSIONTM implants of rational conical angle designs seem to be effective in stress distribution. For all designs and load directions, the upper 1/3 TM implant is the most favorable around the crest.