Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.

Objective:To explore the value of multi-gene copy number variation (CNV) analysis in the clinical prognostic prediction of patients with multiple myeloma (MM).Methods:A retrospective case series study was conducted. The clinical data of 79 MM patients who were admitted to the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to March 2023 were collected. The whole-genome CNV status was obtained by using whole-genome low depth sequencing (sWGS) of bone marrow blood cells. The outcomes of remission, minimal residual disease (MRD) turning negative, progression-free survival (PFS) and overall survival (OS) in patients with and without CNV were compared. The Cox proportional hazards model was used to analyze the influencing factors of PFS and OS.Results:Among the 79 patients with MM, 43 were males and 36 were females. The median age [ M ( Q1, Q3)] was 65 years old (55 years old, 71 years old). In the revised international staging system, there were 20, 51 and 8 cases in stage Ⅰ, Ⅱ and Ⅲ, respectively. The results of fluorescence in situ hybridization (FISH) were abnormal in 17 cases. CNV was detected in 55 patients (69.6%), and the abnormality of chromosome 1q (27 cases, 49.1%) was the most frequently detected, followed by the abnormality of chromosome 13 (26 cases, 47.3%), chromosome 6 (22 cases, 40.0%), chromosome 11 (19 cases, 34.5%), chromosome 8 (18 cases, 32.7%), chromosome 14 (14 cases, 25.5%), and chromosome 17 (11 cases, 20.0%). The ≥ very good partial remission rate in the detected CNV group was lower than that in the undetected CNV group [29.1% (16/55) vs. 45.8% (11/24)], but the difference was not statistically significant ( χ2 = 2.08, P = 0.149). The MRD negative conversion rate of detected CNV group was lower than that of undetected CNV group [21.8% (12/55) vs. 58.3% (14/24)], and the difference was statistically significant ( χ2 = 10.09, P = 0.001). Survival analysis showed that PFS in the detected CNV group was worse than in the undetected CNV group [median PFS time: 36.7 months (95% CI: 6.1-67.4 months) vs. not reached], and the difference between the two groups was statistically significant ( χ2 = 6.61, P = 0.010), while the difference in OS between the two groups was not statistically significant ( χ2 = 1.84, P = 0.175). There was no significant difference in PFS and OS between patients with 1 and ≥2 abnormal copy sequences (both P > 0.05). PFS of patients with CNV on chromosomes 1q, 17, 8, 11 and 13 was worse than that of patients without CNV at these sites (all P < 0.05), while there was no statistical difference in OS (all P > 0.05). Results of univariate analysis showed that lactate dehydrogenase (LDH) level was correlated with PFS and OS of patients (both P < 0.05), and CNV was correlated with PFS of patients (P = 0.010). Results of multivariate analysis showed that LDH > 250 U/L was an independent factor for poor PFS and OS of patients ( HR = 0.135, 95% CI: 0.019-0.983, P = 0.048; HR = 0.132, 95% CI: 0.018-0.951, P = 0.045). Conclusions:Multi-gene CNV analysis can assist in predicting the prognosis of MM patients, and it is more sensitive than traditional CNV detection methods such as FISH. Patients with CNV on chromosomes 1q, 17, 8, 11, and 13 have poor prognosis.

Objective:To investigate the epidemiological characteristics of hospitalized children with respiratory syncytial virus (RSV)-associated acute lower respiratory tract infection (ALRTI), and to analyzed the risk factors for severe infection.Methods:The epidemiological and clinical data of hospitalized children with ALRTI and positive RSV test from Children′s Hospital of Fudan University from January 2013 to December 2018 were retrospectively analyzed.The hospitalized children from October 2016 to November 2017 were selected by random singular sequence and divided into severe infection group and non-severe infection group. The clinical data of the two groups were compared. Multivariate logistic regression analysis was used to analyze the risk factors of severe RSV-associated ALRTI.Results:A total of 34 192 hospitalized children were diagnosed with ALRTI, and 8 113(23.73%) children were positive for respiratory tract viruses, including 4 028(11.78%) children with RSV infection, which was higher than other common respiratory tract viruses. Among the 4 028 RSV-positive children, 2 550(63.31%) were under six months of age, 3 623(89.95%) were under two years of age. The detection rates of RSV in spring, summer, autumn and winter were 6.47%(553/8 551), 2.46%(176/7 161), 12.85%(1 042/8 111) and 21.77%(2 257/10 369), respectively. In 347 hospitalized children with RSV-associated ALRTI, 54 cases were severe cases. Multivariate logistic regression analysis showed that RSV-positive patients complicated with respiratory diseases ( Z=3.43), cardiovascular diseases ( Z=4.96), non-exclusive breast-feeding ( Z=-1.97) and premature birth ( Z=-1.98) were independent risk factors for severe RSV-associated ALRTI (all P<0.050). Conclusions:RSV is the most important and common viral pathogen in hospitalized children with ALRTI in Shanghai, and infants under six months of age are the most susceptible to RSV. RSV patients complicated with respiratory diseases, cardiovascular diseases, non-exclusive breast-feeding and premature birth are more likely to develope severe RSV-associated ALRTI.

Objective:To describe the clinical features of liver involvement in children and adolescent with 2019-nCoV infection.Methods:The clinical data of 77 hospitalized cases admitted to the Children’s Hospital of Fudan University were collected from January 19 to November 28, 2020. The characteristics and risk factors of abnormal liver chemistries in children with laboratory-confirmed 2019-nCoV infection were analyzed.Results:Of the 77 cases, 44 were male (57.1%) and 33 were female (42.9%), with a median age of 10 years. 27(35.1%) were asymptomatic, 28(36.4%) had mild illness, 22(28.6%)had non-severe pneumonia. Hydroxychloroquine was used in 7 cases. Of the 75 children without underlying diseases, alanine aminotransferase was elevated in 1 case (1.5%, during hydroxychloroquine therapy), aspartate aminotransferase was elevated in 7 cases (10.3%), alkaline phosphatase was elevated in 7 cases (28%), and total bilirubin, direct bilirubin, albumin, international normalized ratio were in normal range. There was no statistical difference between the pneumonia group and the non-pneumonia group in term of liver chemistries ( P > 0.05), same as between the elevated erythrocyte sedimentation rate group and the normal group. There was no aggravation of liver injury in the child with biliary atresia. The child with epilepsy showed no abnormal liver chemistries after infection. Conclusion:Children with 2019-nCoV infection had mild clinical symptoms with few cases of liver injury. The abnormal liver chemistries in children with COVID-19 infection may be related to the underlying disease and the use of antiviral drugs.

Objective:To monitor the epidemiological characteristics of viral etiology in children with influenza-like illness and to guide the prevention and management of acute respiratory tract infections in childhood.Methods:Nasopharyngeal swabs were collected from the outpatient children seeking medical care in Children′s Hospital of Fudan University, Shanghai for influenza-like illness between January 2015 and December 2018. Multiplex real-time polymerase chain reaction was performed to detect respiratory syncytial virus (RSV), influenza virus (Flu), adenovirus (ADV), parainfluenza virus (PIV, type Ⅰ to type Ⅳ) and enterovirus (EV), and the epidemiological data were analyzed. Chi-square test was used for statistical analysis.Results:A total of 2 271 patients with influenza-like illness were enrolled, age range from two months to 182 months old, 1 280 cases(56.4%) were positive for the target respiratory viruses tested on respiratory samples. The detection rates of FluA, FluB, PIV, EV, ADV, RSV were 15.1%(343/2 271), 12.5%(284/2 271), 8.4%(191/2 271), 7.8%(177/2 271), 5.1%(116/2 271) and 6.7%(152/2 271), respectively.The detection rates of influenza virus were statistically different among the age groups ( χ2=39.33, P<0.05), which showed an increasing trend with the increasing ages. The detection rate of RSV was 9.7%(35/361) in infant group from zero to 12 months old, which was higher than other age groups. Usually, FluA had two epidemic peaks during the winter and summer seasons, the epidemics of FluB and RSV peaked during the winter season, and EV and PIV were more prevalent in the summer season. Conclusions:Influenza virus remains the most common viral pathogen responsible for childhood influenza-like illness in Shanghai.Influenza virus has high incidence in winter.Widely influenza vaccination is highly recommended for the effective prevention the influenza outbreaks.Continuous monitoring the epidemic trend of viral respiratory infections is imperative for the prevention and control of diseases.

Objective To monitor the clinical epidemiology and etiology of acute diarrhea in children in the outpatient setting in Shanghai .Methods An active surveillance study in Children′s Hospital of Fudan University between August 2013 and July 2014 was conducted .Outpatient children with acute diarrhea were enrolled in this study and stool samples were collected .Pathogens including norovirus ,diarrheagenic Escherichia coli (DEC) , nontyphoidal Salmonella spp .(NTS),Campylobacter,Shigella,pathogenic vibrio and Yersinia enterocolitica were identified and typed .The χ2 test was used for statistical analysis .Results Of the 881 stool samples from enrolled children , the pathogens included into the target detection were identified in 246 (27 .92% ) cases . Norovirus ,DEC ,NTS ,Campylobacter and Shigella were detected in 98 (11 .12% ) cases ,74 (8 .40% ) cases , 61 (6 .92% ) cases ,34 (3 .86% ) cases and 2 (0 .23% ) cases ,respectively .Neither pathogenic vibrio nor Yersinia enterocolitica was identified .Children younger than 36 months old (3 .27% ,26/794) had a lower risk (χ2=7 .41 ,P=0 .006) of Campylobacter infection compared with older children (9 .20% ,8/87) .Vomiting (37 .76% ) and watery diarrhea (21 .34% ) were more commonly seen in children with norovirus infection;fever and mucous stool were commonly seen in diarrheal children with NTS infection (40 .98% and 21 .31% ,respectively) and Campylobacter infection (29 .41% and 26 .47% ,respectively) .Conclusion Enteric pathogens play a major role in childhood acute diarrhea in Shanghai .Continuous monitoring of enteric pathogens will be helpful for reasonable treatment and prevention of acute diarrhea in children .

Objective To monitor the epidemic pattern of influenza in children during the 2011-2012 season in Shanghai and to evaluate the socioeconomic burden of influenza in children.Methods We carried out a prospective surveillance program on influenza among children who visiting the outpatient clinic for influenza-like illness (ILI) between June 2011 and May 2012.Respiratory samples as well as related demographic and clinical data were obtained from the enrolled cases.Socio-economic burden was evaluated using the questionnaires for some of the confirmed cases during the outbreak.Results Out of the 1 119 enrolled cases,influenza viruses were virologically confirmed,using the RT-PCR in 370 (33.1％) otherwise healthy children.Among them,109 (9.7％) were positive for influenza A/H3N2 viruses,and 279 (24.9％) were positive for influenza B viruses.The 2011-2012 seasonal outbreak of influenza among children with Shanghai residency started with the major outbreak of influenza B during December 2011-Feburary 2012,followed by the smaller outbreak of influenza A/H3N2 during March-April,2012.A total of 69 influenza A/H3N2-infected cases and 163 influenza B-infected cases were surveyed to evaluate the influenza-associated disease burden.The average costs per case were 706.10 Yuan and the average indirect costs per case incurred by the work loss of family members were 293.80 Yuan,with the total average costs per case were 999.90 Yuan.Mean visits to medical settings were 2.7,with antibiotics used in 67.2％ of the cases.Secondary household cases were seen in 21.1％ of the cases.Pneumonia was diagnosed in 5.6％ of the cases.The burden of disease increased from both influenza A/H3N2 and influenza B but without significant differences between them.Conclusion Influenza A/H3N2 and influenza B viruses caused outbreaks of influenza in children with Shanghai residency during the 2011-2012 season.Socioeconomic burden of influenza in children showed significantly direct impact on the sick children and an indirect impact on their families.Influenza vaccination should be recommended in children to reduce the disease burden.

Objective To evaluate the features of optical molecular imaging of bladder tumor cells labeled by tumor homing peptide fluorescent molecular probe, and to explore the theoretical foundation of optical molecular imaging for bladder cancer diagnosis.Methods After prepared the FITC-CSNRDARRC fluorescent molecular probe, laser scanning confocal microscope, immuno fluorescence and multispectral fluorescence in vivo optical molecular imaging system have been used to evaluate the binding sites, the affecting factors of binding rates, the specificity and the targets.BIU-87 bladder tumor cell line, BIU-87 bladder tumor cell line, 68 cases of paraffin bladder tumor tissue samples, 16 cases of paraffin glandular bladder inflammatory samples, 43 cases of paraffin renal clear cell carcinoma samples, 68 cases of paraffin gastric adenocarcinoma samples, 29 cases of urine exfoliated cells suspected bladder cancer and BIU-87 bladder cancer nude xenograft have been used in this study.Results The binding site of FITC-CSNRDARRC fluorescent molecular probe were at the nucleus of labeled bladder tumor cells.The binding rates were correlated linearly with the dose of probe and the grade of pathology.The in vitro and in vivo studies demonstrate that the probe has a binding specificity with bladder tumor. When the FITC-CSNRDARRC fluorescent molecular probe labeled tumor cells, bright green spots were observed under laser scanning confocal microscope.The bright green spots were more apparent after stained by DAPI again.The tissue samples and tumor cells in the urine can be successful labeled and identified by fluorescence microscope.Optical molecular imaging of in vivo xenograft tumor tissues showed fluorescent spots under EMCCD.Conclusions The labeled loci of single cell by FITC-CSNRDARRC probe have been identified. The spatial resolution of optical molecular image is related to sensitivity of CCD, and the optical molecular imaging cannot be imaged by the conventional endoscope camera.