ObjectiveTo explore the biological mechanism of bone loss caused by perfluorooctanoic acid (PFOA) through transcriptomic analysis, and to provide new insights into regulating perfluoroalkyl substances (PFAS) applications and the prevention of hazards affecting bone health. MethodsMouse embryonic osteoblast precursor cells (MC3T3-E1) were exposed to 0.1, 1, 10, and 100 μmol·L^-¹ PFOA for 24 hours to assess the effects on cell viability and alkaline phosphatase (ALP) activity, and to determine the critical concentration of PFOA toxicity. The transcriptome sequencing (RNA-seq) was performed to identify differentially expressed genes (DEGs) induced by PFOA. Gene ontology (GO) analysis and gene set enrichment analysis (GSEA) were conducted to identify significantly affected gene pathways. Additionally, Seahorse XF metabolic phenotyping and reverse transcription polymerase chain reaction (RT-PCR) were used to validate the key pathways. ResultsExposure to 10 and 100 μmol·L^-¹ PFOA significantly reduced the cell viability and ALP activity of MC3T3-E1 cells. Therefore, the results of transcriptomic analysis for 10 μmol‧L^-1 PFOA exposure found that a total of 80 DEGs were identified, including 32 upregulated genes and 48 downregulated genes. According to GO analysis, PFOA mainly affected cellular components such as mitochondrion and nucleus, molecular functions involving GTPase activity and GTP binding, as well as biological process related to mRNA processing. GSEA identified the downregulation of the β-oxidation of fatty acid pathway in mitochondria. Metabolic phenotyping reserches showed that PFOA indeed reduced mitochondrial aerobic respiration capacity and adenosine triphosphate (ATP) production, and the ratio of ATP production from cellular aerobic respiration to glycolysis was significantly decreased as well. The mRNA expression of glucose metabolism-related genes (GK, G6PD, and CS), as well as fatty acid metabolism-related genes (CPT1A and CPT2), were significantly downregulated. ConclusionPFOA reduces bone formation by inhibiting energy metabolism and β-oxidation of fatty acid pathways in osteoblasts, whihc lays the foundation for revealing the mechanism of PFOA exposure induced bone loss.

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

BACKGROUND:The pedicle navigation template has many advantages,but there are still some problems.For example,poor soft tissue dissection leads to poor adhesion of the pedicle navigation template,resulting in screw path deviation;careful dissection of soft tissue to fit the pedicle navigation template leads to prolonged surgery time and increased bleeding;the design of the pedicle navigation template cannot predict the vertebral rotation and the impact of body position changes,resulting in the poor fitting. OBJECTIVE:To explore the utility of a new 5-point positioning point-contact pedicle navigation template in the case of scoliosis and complex pedicle. METHODS:A total of 20 patients with scoliosis and complicated pedicle admitted to the Department of Spinal Surgery,Guizhou Hospital,Beijing Jishuitan Hospital from February 2020 to February 2023 were selected for scoliosis orthopedics.During the operation,the 5-point positioning point-contact pedicle navigation template was used to guide the screws.According to the inclusion and exclusion criteria,34 cases were matched as the empirical nail placement group,and conventional barehanded nail placement was performed.The time of placement,the amount of bleeding,the number of fluoroscopies,the number of manual diversions,the level and accuracy of pedicle screws,the complications of placement,and the rate of correction of main curvature were compared between the two groups. RESULTS AND CONCLUSION:(1)There were no significant differences in sex,age,coronal Cobb's angle of the main curvature,bending Cobb's angle of the main curvature,pedicle variation,apex rotation,fusion segment,number of screws,level of screws,accuracy of screws,and rate of correction of main curvature between the navigation template group and the empirical nail placement group(P>0.05).(2)Compared with the empirical nail placement group,the navigation template group had more advantages in time of placement(P=0.034),amount of bleeding(P=0.036),number of fluoroscopies(P=0.000)and number of manual diversions(P=0.021).(3)There were 0 cases of screw-related complications in both groups.(4)In conclusion,the 5-point positioning point-contact 3D printing pedicle navigation template has a claw-like structure.It can firmly adapt to various deformities of the lamina articular process,avoid drift,and accurately place the screws.It has a point-like contact lamina structure to avoid extensive and complete dissection of the posterior structure,and reduce bleeding,operation time,and trauma.Pre-designed screw entry points and directions can reduce the number of fluoroscopy and operation time.Segmental design can avoid discomfort due to changes in anesthesia position.The operation is simple and the accuracy of screw placement is high.

ObjectiveTo establish a non-targeted screening method for emerging contaminants in drinking water based on high-resolution mass spectrometry and apply it to actual water samples. MethodsA total of 9 drinking water samples collected from 3 reservoirs in Shanghai were purified and concentrated by HLB solid phase extraction column， then separated and analyzed by liquid chromatography high-resolution mass spectrometer and gas chromatography high⁃resolution mass spectrometer. The acquired data were analyzed by Thermo Tracefinder， Excel and other software combined with mzCloud and NIST databases. The methodology was verified with representative compound standards. Pesticide and perfluorinated compounds were taken as examples to analyze their pollution status. ResultsA non-targeted analysis strategy based on liquid chromatography and gas chromatography tandem high-resolution mass spectrometry was established. The pollution level of 20 kinds of pesticides and 4 kinds of perfluorinated compounds identified in 9 drinking water samples were higher in the Huangpu River than in the Yangtze River estuary. ConclusionThe established non-targeted screening method by high-resolution mass spectrometry can detect potential emerging contaminants in drinking water without relying on the standards， which provides a powerful technical means for water quality monitoring and risk assessment.

Per- and polyfluoroalkyl substances （PFASs） are a new type of persistent organic pollutants with global attention. They have shown multiple toxic effects due to their persistent accumulation in human body through exposure to environmental media such as drinking water， food， atmosphere， and soil. However， the bone toxicity of PFASs has not attracted enough attention. It is believed that the exposure and accumulation of PFASs in human have a significant impact on the bone health， especially hindering the healthy bone development in infants and adolescents， and aggravating the occurrence of bone loss and fracture in the elder populations. This paper will review the research progress of the effects of PFASs exposure on bone health indicators such as bone mineral density， and discuss the mechanisms of PFAS in bone toxicity. This review will provide references for revealing the effects of PFASs exposure on bone health and their toxic mechanisms.

Objective:To summarize the clinical experience and effect of applying 3D printing assisted with the technology of extracorporeal pre-fenestration in the treatment of thoracic/abdominal aortic aneurysm.Methods:From August 2019 to November 2020, 15 patients with thoracic/abdominal aneurysm involving visceral arteries were admitted to our center, including 11 males and 4 females, with mean age of 57-82(68.26 ±4.73) years old. According to diameters of visceral artery, thoracic aorta, abdominal aorta, and bilateral iliac arteries measured by CTA, we selected suitable stents and made a 3D printing model by professional software to guide the position of intraoperative external fenestration and the fenestration diameter to implement full cavity repair.Results:All operations were completed and one case was converted to laparotomy. The average time of operations was(200.67±41.00)min and hospital stay was(13.47±4.16)days without any death, organ failure, endoleak, paraplegia, graft infection and other complications.Conclusion:The application of 3D printing assisted with the technology of extracorporeal pre-fenestration in the treatment of thoracic/abdominal aortic aneurysm is feasible and effective, and the short-term results are satisfactory.

Objective: The purpose of this study was to explore the application value of digital surgery in the reconstruction of mandibular composite defects with a chimeric deep circumflex iliac artery perforator flap (DCIAPF). Methods: Six patients with complex defects within half of the mandible underwent reconstruction using DCIAPF from January 2019 to January 2020 in Shenzhen People’s Hospital. Doppler was used to locate the deep iliac circumflex artery, the range of mandibular osteotomy was designed, and DCIAPF was used to repair the mandibular composite under the guidance of the guide plate during the operation. Twelve months postoperatively, the facial shape, jaw height, and occlusal relationship were evaluated Results: DCIAPF was harvested successfully in 6 patients, and the heights of all alveolar ridges and occlusal function of patients were significantly restored, without pain or snapping in the temporomandibular joint area. Conclusion The blood supply of DCIAPF is rich, and soft-bone tissue is sufficient for the reconstruction of mandibular composite defects. Combined with digital surgery, the accuracy and safety are improved.

Objective:To establish a supportive and effective management mode of scientific research project application, promote the capacity building of scientific research in the hospital.Methods:Retrospective analysis was conducted on the national and provincial scientific research projects of Xinhua Hospital Affiliated to Shanghai Jiaotong University Medical School from 2010 to 2019, and the practical effect of " point to point" management mode of scientific research project application was evaluated.Results:The funding rate of Xinhua Hospital, especially national scientific research projects and provincial talents projects, was greatly improved by adoption of the multi-dimensional " point to point" management mode of scientific research project application. The number of national scientific research projects increased from 34 (26.02 million) in 2010 to 72 (51.0851 million) in 2019.The number of provincial talents projects increased from 5 (1.05 million) in 2010 to 26 (6.5 million) in 2019.Conclusions:The " point to point" management mode of scientific research project application plays an important role in promoting the overall funding rate. Enhancement of comprehensive capacity of hospital scientific research can be achieved by further improvement of this management mode, early initiation and arrangement of funding application depending on the " close partner" entity, emphasizing scientific research talents cultivation.

Objective:To investigate pediatric sepsis-related mortality of pediatric intensive care unit(PICU) and family socioeconomic status in Yangtze River Delta.Methods:A prospective, multicenter observational study was conducted to collect sepsis cases from eight PICUs in Jiangsu, Zhejiang and Shanghai from August 2016 to July 2017.Sepsis cases were divided into normal sepsis group and severe sepsis group.The primary outcome was in-hospital death.Patient data were prospectively collected including age, gender, medical insurance status, long-term residence, source of admission, first-day pediatric sequential organ failure score(pSOFA) score, underlying diseases and socioeconomic characteristics including family education level, family annual economic income.Results:A total of 4, 983 patients admitted in PICUs, of which 651 patients were diagnosed sepsis on admission.The prevalence of sepsis was 13.1% (651/4 983), and overall mortality was 11.7% (76/651). The prevalence of severe sepsis was 28.3% (184/651), and the mortality was 20.1% (37/184). The overall median age was 0.9 years old.The infant group accounted for 50.8%, including 331 cases, followed by toddler group 19.8% (129 cases), preschool group 13.0% (86 cases), school group 11.8% (77 cases), and adolescent group 4.3% (28 cases). The median pSOFA score was 4.Logistic regression analysis showed that the OR value was 1.4(95% CI 1.3-1.5) of pSOFA score corresponding to the death of sepsis in hospital.There were 14.6% patients left hospital in medical insurance group, while 27.4% in non-medical insurance group, and there was significant difference between these two groups.The median of daily cost was 5, 446 RMB, among which the median of daily cost of sever sepsis was 6, 678 RMB.The median of total cost for sepsis was 36, 109 RMB, and that for severe sepsis was 41, 433 RMB. Conclusion:The sepsis-related mortality was high in PICU.The pSOFA score has a certain predictive value for the prognosis of sepsis.The burden of sepsis is still heavy.Compared with medical insurance families, non-medical insurance families have a higher proportion of choosing left hospital.

Objective To investigate the effects of xenogenic bone with chitosan/norvancomycin sustained-release biomaterials in treating infectious bone defects in rabbits.Methods Xenogenic bone with chitosan/norvancomycin sustained-release biomaterials was made by electrospinning technique.Rabbit infectious bone defect models were made by Methicillin-resistant Staphylococcus aureus.A successful model was evaluated with the standard of more than three points in Norden score assessment.All models were divided into two groups by random number table method,with eight models in each.The control group was treated with surgical debridement,and the experimental group was implanted with bone particles of xenogenic bone with chitosan/norvancomycin sustained-release system after debridement.Postoperatively,general conditions,X-ray,histological results of HE staining,and bacteriological examination results of the rabbits were observed.Results X-ray showed significant bone defects,sequestration,periosteal reaction,and soft tissue swelling after one month of modeling,with Norden score of (3.84 ± 0.52) points.The general conditions were good and the sinus tracts were healed in experimental group after two months of treatment.The control group demonstrated generally poor conditions with swollen sinus and purulent discharge.Two rabbits were died of sepsis.The pathological scores of tibial were (0.41 ± 0.08) points in experimental group,and (3.27 ± 0.26) points in control group by gross observation.The pathological score of experimental group was significantly lower than control group(P ＜ 0.05).The bone defects were basically repaired in experimental group.The longest diameter of bone defect in experimental group was (0.11 ± 0.02)cm,significantly smaller than (0.48 ± 0.06) cm in control group (P ＜ 0.05).There were no obvious signs of osteomyelitis and the bone defects were well repaired in experimental group.Periosteal reaction,soft tissue swelling,a substantial number of bone destruction,and sequestration were observed in control group.The Norden score was (1.32 ± 0.23) points in experimental group,lower than (5.21 ± 0.48) points in control group(P ＜ 0.05).HE staining showed a large amount of trabecular bone formation,bone cell formation,and fibrous hyperplasia in experimental group,with no obvious signs of infection.On the other hand,infiltration of inflammatory cells,necrotic tissue,and sequestration were observed in control group.The histological score was(0.61 ± 0.10) points in experimental group,lower than (4.21 ± 0.41) points in control group (P ＜0.05).The negative rate of bacterial culture in experimental group was 33％,lower than 100％ in control group (P ＜ 0.05).Conclusion Xenogenic bone with ehitosan/norvancomycin sustained-release biomaterials has excellent effect in infection clearance and bone defect reparation in treatment of infectious bone defects in rabbits.