Objective To explore the effect of rotenone exposure on the metabolic homeostasis of nicotinamide adenine dinucleotide(NAD+)in dopaminergic neurons of the rat mid-brain striatum,and investigate the effect of exogenous NAD+intervention on the cellular damage response of dopaminergic neurons induced by rotenone.Methods Male SD rats(8 weeks old,200～250 g)were divided into a control group using a table of random numbers,a rotenone exposure group,an NAD+-intervention group,and an NAD+group.An intoxication model was established in the rotenone exposure group.NAD+(250 mg/kg)was administered simultaneously with rotenone exposure in the NAD+-intervention group.The NAD+group was only given NAD+,while the control group received no intervention.After modeling,open field test was performed to evaluate behavioral changes.After scarification,serum samples and mid-brain striatal tissues were collected.HE staining was used to observe the morphology of dopaminergic neurons in the striatum.The NAD+content in the tissues was detected with NAD+/NADH kit.Western blotting was employed to determine the contents of tyrosine hydroxylase(TH),nicotinamide phosphoribosyltransferase(NAMPT),nicotinamide mononucleotide adenylyltransferase(NMNAT),and solute carrier family 25 member A51(SLC25A51).ELISA was utilized to measure the content of dopamine in the striatal tissues.Immunohistochemical staining was applied to observe the distribution and contents of TH proteins in the striatal tissues of each group.Results Rotenone exposure significantly affected the vital signs and motor abilities of rats,induced disorderly-arranged,atrophy and deformed neurons in the striatal tissue,decreased the content of TH,rate-limiting enzyme for dopamine synthesis,by approximately 29%(P<0.01),the content of dopamine by about 42%,and that of NAD+by almost 50%(P<0.01),while increased the NADH/NAD+ratio(P<0.01).After exposure,the content of NAMPT,an enzyme related to NAD+synthesis,was decreased by 26%(P<0.05),the contents of NMNAT1-3 and SLC25A51,mitochondrial transporters of NAD+by approximately 21%,38%,43%,and 21%,respectively(P<0.01).Exogenous NAD+intervention improved the motor function of exposure rats and the morphology of dopaminergic neurons in the mid-brain striatal tissue,and restored the content of TH in the striatal tissue significantly by 12.8%(P<0.05),and the content of dopamine by 20.9%(P<0.05).Conclusion Rotenone disrupts the NAD+homeostasis in dopaminergic neurons by inhibiting the NAD+synthesis and transport pathways in the mid-brain striatal tissues,while exogenous NAD+intervention can effectively alleviate the dopaminergic neuron damage induced by rotenone exposure.

Objective:To identify the risk factors for failure in closed reduction of flexed supracondylar humerus fractures of Wilkins type Ⅲ in children.Methods:The data of 171 children were retrospectively analyzed who had been treated for flexed supracondylar humerus fractures of Wilkins type Ⅲ from January 2013 to December 2021 at Department of Orthopaedics, Children's Hospital of Jiangxi Province and Children's Hospital of Fudan University Anhui Hospital. They were divided into a reduction failure group (35 cases) and a reduction success group (136 cases). Factors such as fracture height, age, body mass index, ulnar-radial offset direction, obvious axial rotation of the distal fracture fragment, combined ulnar nerve injury, and time from injury to operation were listed as risk factors. The independent risk factors for failure in closed reduction of flexed supracondylar humerus fractures were identified by univariate analysis of variance and multi-variate logistic regression analysis.Results:The average age of 171 children was (7.8±2.6) years. There were 151 cases of radial deviation and 20 cases of ulnar deviation, 120 high type fractures and 51 low type fractures, and 20 cases of combined ulnar nerve injury and 115 cases of obvious rotation of the distal fracture fragment. The one-way ANOVA showed statistically significant differences between the reduction failure group and the reduction success group in terms of age, obvious rotation of the distal fracture fragment, and ulnar nerve injury ( P<0.05), but no significant differences in fracture height, body mass index, ulnar-radial offset direction, or time from injury to operation ( P>0.05). Multivariate logistic regression analysis showed that obvious rotation of the distal fracture fragment ( OR=3.287, 95% CI: 1.136 to 9.513, P=0.028) and combined ulnar nerve injury ( OR=6.439, 95% CI: 2.262 to 18.327, P=0.001) were risk factors for failure in closed reduction. Conclusion:As obvious rotation of the distal fracture fragment and combined ulnar nerve injury may be independent risk factors for failure in closed reduction of flexed supracondylar humerus fractures of Wilkins type Ⅲ in children, they should arouse more attention in the treatment of such fractures.

Objective:To investigate the characteristics and reliability of a novel sub-classification of Wilkins type III lateral-flexion supracondylar fracture of the humerus in children.Methods:A retrospective cohort study was used to analyze the clinical data of 92 children with supracondylar fracture of the humerus admitted to Provincial Children′s Hospital of Anhui Medical University from January 2013 to August 2021, including 38 males and 54 females, aged 2-13 years [(8.5±2.4)years]. Lateral-flexion Wilkins type III supracondylar humeral fractures were classified into two subtypes according to the fracture features: type IIIA ( n=14), complete fracture with the distal fragment displaced anteriorly and laterally, with no obvious anterior or posterior inclination (<10°) or rotation; type IIIB ( n=78), complete fracture with the distal fragment displaced anteriorly and laterally, with significant anterior or posterior inclination (>10°) or rotation. The incidence and risk ratio of ulnar nerve injury and open reduction were compared between the two subtypes of the fracture. The weighted Kappa method was used to test the inter- and intra-observer agreement of the two new subtypes. Results:Of all, 15 children had ulnar nerve injury, among which 1(6.7%) was type IIIA and 14(93.3%) were type IIIB; while other 77 children had no ulnar nerve injury. The risk of ulnar nerve injury in children with type IIIB was 3-fold higher than that in children with type IIIA ( OR=2.84, 95% CI 0.34- 25.56, P>0.05). The open reduction was performed in 11(73.3%) out of the 15 children with ulnar nerve injury, but in 18(23.4%) out of the 77 children with no ulnar nerve injury. The risk of open reduction in children with ulnar nerve injury was 9-fold higher than that in children without ulnar nerve injury ( OR=9.01, 95% CI 2.28- 33.17, P<0.01). Open reduction was performed in 29 children, among which 2(6.9%) were type IIIA and 27(93.1%) were type IIIB. The risk of open reduction in children with type IIIB was 3-fold higher than that in children with type IIIA ( OR=3.17, 95% CI 0.66-15.24, P>0.05). The intra-observer Kappa value was 0.49±0.09(95% CI 0.31-0.66), indicating a moderate agreement. The inter-observer Kappa value was 0.80±0.06(95% CI 0.68-0.91), indicating a strong or very strong agreement. Conclusions:Wilkins type IIIB lateral-flexion supracondylar fracture of the humerus in children is more likely to be accompanied by ulnar nerve injury and to be opt to open reduction in comparion with type IIIA. The new subtyping has reliable inter-observer and intra-observer consistency, and is able to facilitate the prediction of surgical plans.

Objective:To investigate the correlation of endoscopy findings with symptoms in patients undergoing gastroscopy.Methods:Patients who underwent gastroscopy for the first time in Renji Hospital of Shanghai Jiao Tong University School of Medicine from January to December 2017 were included in the questionnaire survey. The participants were asked to report their main symptoms of the digestive tract in details, and gastroscopy was completed within 2 weeks. Final gastroscopic diagnosis was made based on both gastroscopy and pathology, then patients were divided into the major-lesion (peptic ulcer and malignancy) group and the non-major-lesion (chronic gastritis, reflux esophagitis and others) group. The correlation of gastrointestinal symptoms with gastroscopic findings was analyzed. The risk for major gastroscopic lesions (peptic ulcer and malignant tumors) was assessed by multivariate Logistic regression analysis.Results:A total of 5 885 patients completed the questionnaire, 5 496 (93.4%) of whom completed gastroscopy. The detection rates of peptic ulcer were 12.3% (373/3 028), 12.6% (52/412), 17.9% (49/273), 9.5% (64/675) and 9.2% (102/1 108) in patients with dyspepsia, reflux, alarm, other symptoms and no symptoms, respectively, the detection rates of malignant tumors were 1.2% (36/3 028), 0.7% (3/412), 7.7% (21/273), 0.7% (5/675) and 0.4% (4/1 108), respectively in these patients. The most common symptoms was dyspepsia, accounted for 58.3% (373/640) and 52.2% (36/69) patients with peptic ulcer and malignant tumors, respectively. Alarm symptoms were found in 30.4% (21/69) patients with malignant tumors, and 15.9% (102/640) peptic ulcer patients and 5.8% (4/69) malignant tumor patients had no gastrointestinal symptoms. Compared to asymptomatic individuals, patients with dyspepsia ( P<0.001, OR=1.52, 95% CI: 1.21-1.92) and those with warning symptoms ( P<0.001, OR=2.87, 95% CI: 2.02-4.08) had significantly increased risk for major lesions (peptic ulcer and malignant tumors) detected by gastroscopy. Conclusion:Although dyspepsia and alarm symptoms are positively associated with upper gastrointestinal malignancy and peptic ulcer, they are of limited predictive value for upper gastrointestinal diseases.

Objective:To explore the efficacy and safety of neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients.Methods:Six patients with NSCLC who were diagnosed as ⅢA and received two cycles of neoadjuvant chemoimmunotherapy and surgery between September 2019 and January 2020 were described in this study.Results:Five of them experienced AEs during neoadjuvant therapy. All of them received surgery and achieved an MPR of 50%. No viable tumor cells were found in the tissues of one patient. One patient with a small bronchopleural fistula after lobectomy.Conclusion:Neoadjuvant chemoimmunotherapy combined with surgery for stage ⅢA NSCLC patients is safe and efficient. Long-term outcomes of neoadjuvant chemoimmunotherapy combined with surgery should be further validated.

Objective To observe the intervention effect of immune-enhancing enteral nutrition (EN) emulsion on immune function of critically ill patients with mechanical ventilation (MV). Methods One hundred and twenty critically ill patients with MV admitted to the Department of Emergency Intensive Care Unit (EICU) of Taizhou First People's Hospital from July 2015 to June 2017 were enrolled, and they were divided into immune-enhancing EN group and standard EN group by random numbers generated by a computer. Ultimately, 76 cases were enrolled in the study, among them, 36 cases were in the immune-enhancing nutrition group and 40 cases were in the standard nutrition group. The differences of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ), the sequential organ function evaluation (SOFA) score on 1, 3, 7 days and immunity indexes (secretory immuno-globulins IgA, IgG, IgM), lymphocyte subpopulation (CD4 and CD8), duration of MV and the length of ICU stay on the 1, 7 days after EN were compared. Results Comparisons between the immune-enhancing EN group and standard EN group showed: APACHE Ⅱ score had no statistically significant difference between the two groups at each time point, SOFA score on 7 days after EN treatment was significantly decreased in the immune-enhancing EN group (2.56±1.38 vs. 3.68±2.96, P < 0.05); IgA, IgG, IgM were obviously higher in the immune-enhancing EN group than those in standard EN group on 7 days after treatment [IgA (mg/L): 2 967.6±635.6 vs. 2 525.0±592.7, IgG (mg/L): 14 982.5±2 899.7 vs. 12 996.4±2 875.9, IgM (mg/L): 1 206.8±233.3 vs. 1 093.2±165.1, all P < 0.05], CD4 (0.45±0.06 vs 0.37± 0.10) and CD8 (0.20±0.03 vs. 0.18±0.04) were significantly higher than those in standard EN group (both P < 0.05). The MV time (hours): 122.33±63.91 vs. 155.69±77.06) and ICU stay time (hours): 197.57±70.60 vs. 239.61±84.83) of the immuno-enhancing EN group were markedly shorter than those of the standard EN group (both P < 0.05). Conclusion Compared with standard EN, the immune-enhancing EN emulsion can improve the immune function of critically ill patients with MV, and shorten the duration of MV support and the length of ICU stay.

Objective To establish the lung cancer cell strain with low ATG5 expression and to detect the effect of celastrol on lung cancer cell apoptosis after downregulation of autophagy.Methods H1299 was infected by lentivirus-mediated ATG5 shRNA.RT-qPCR and Western blot assays were applied to confirm the effect of ATG5 knock down.Autophagy was measured by Western blot and RFP-LC3 transfection.Cell apoptosis of ATG5 normal expression group and of ATG5 low expression group of H1299 cells was detected by FACS.Finally, Western blot was used to detect the expression of apoptosis-related proteins Bcl-2, Bax and cleaved caspase-3.Results The expression of ATG mRNA and protein significantly decreased after ATG5 knockdown in H1299 cells (P<0.05).The autophagy marker of LC3-Ⅱ level was downregulated and P62 expression was upregulated after inhibition of ATG5, and the RFP-LC3 puncta reduced significantly after ATG5 knockdown (P<0.05).Compared with control group,the apoptosis rate in ATG5 downregulation group increased significantly after celastrol treatment (P<0.01).Pro-apoptotic proteins of Bax and cleaved caspase-3 levels were upregulated and anti-apoptotic protein of Bcl-2 level decreased after ATG5 inhibition (P<0.05).ConclusionsThe effect of celastrol-induced apoptosis of lung cancer cells was enhanced after downregulation of autophagy, demonstrating inhibition autophay may be a new target of lung cancer treatment.

Objective: To investigate the clinical significance of low-dose CT (LDCT) in coal mine workers with relatively long working years. Methods: A total of 907 coal mine workers with ≥20 working years were enrolled, among whom there were 863 male and 44 female workers with a mean age of 49.5 years. Digital radiography (DR) was performed for these workers in 2013, and LDCT was performed for three consecutive years from 2014 to 2016. Results: A total of 32 workers were found to have lung nodules by DR in 2013, while in 2014, 269 workers were found to have non-calcified lung nodules by LDCT, and there was a significant difference in the number of workers with lung nodules (χ²=233.73, P<0.005) . There was also a significant difference in the detection rate of nodules between the workers with different working years of dust exposure (χ²=6.648, P=0.00) . The male workers had a significantly higher detection rate of nodules than the female workers (χ²=5.690, P=0.017) . There was no significant difference in the number of nodules between workers with different types of work (χ²=16.985, P=0.05) . There were 443 lung nodules in total, among which 71.56% were solid nodules and 55.75% had a size of ≤4mm; malignant nodules were confirmed by surgery in 6 (0.66%) of the 907 workers after baseline LDCT. LDCT reexamination in 2015 and 2016 found new nodules in 8 workers and enlarged nodules in 3 workers, and there was no significant change in the number of nodules with a size of ≤4 mm. Conclusions It is necessary to perform high-risk population screening for coal mine workers by LDCT. The follow-up strategies for nodules with a size of ≤4mm are the same as those for negative results; annual reexamination is recommended for nodules with a size of >4-8 mm, and clinical treatment should be considered for nodules with a size of >8 mm.

In mammals,there are two RNA-binding proteins,Musashi (Msi)1 and Msi2,constituting the Msi family.Msi2 is mainly distributed among neural,hematopoietic,gastrointestinal,pancreatic and epithelial stein cells.It is of great importance to maintain the balance between proliferation and differentiation of stem cells and regulate their growth and development.The changed expression of this protein will induce genesis and progression of malignant tumor through many kinds of signal pathways.Thus,Msi2 is trusted to provide a predictive mark and a therapeutic target for related tumors.