Objective To investigate the protective effect of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) against cisplatin-induced toxicity during antitumor treatment. Methods Specific pathogen-free female SD rats were inoculated with LLC-WRC-256 tumor cells to establish tumor-bearing models, which were randomly divided into the model control group, cisplatin control group, and low-, medium-, and high-dose GMDTC groups, with 10 rats in each group. Another negative control group with 10 rats was included. Rats in the cisplatin control group and the three GMDTC dose groups were injected intravenously with cisplatin at a dose of 5 mg/kg body mass for one time. After 2.0 hours, rats in the three GMDTC dose groups were injected intravenously with GMDTC at doses of 27, 54, and 108 mg/kg body mass, once per day for five consecutive days. Tumor volume, platinum levels in biological samples (whole blood, urine, kidney, and tumor tissue), serum creatinine (Cr) and urea nitrogen (BUN) levels were measured at different time points. The tumor mass was measured, the pathological changes of renal tissue were observed, and the complete blood count was tested. Results The dilation of renal tubules, cell necrosis and shedding, and the formation of renal tubule patterns in the kidneys of rats in the medium- and high-dose GMDTC groups were significantly reduced compared with those in the cisplatin control group. The tumor volume of rats in the cisplatin control group and the three GMDTC dose groups decreased on the 3rd, 5th and 7th days after cisplatin administration, and the tumor weight decreased on the 7th days compared with the model control group (all P<0.05). However, there was no significant difference in the above indexes among the four groups (all P>0.05). The levels of serum Cr and BUN of rats in the cisplatin control group on the 3rd, 5th, and 6th days after cisplatin administration, as well as the score of renal tubular injury degree on the 7th day, were higher than those in the negative control group and the model control group (all P<0.05). The serum Cr levels of rates on the 3rd and 5th days after cisplatin administration, the serum BUN levels on the 5th day in the medium- and high-dose GMDTC groups, the score of renal tubular injury degree, and renal platinum level on the 7th day decreased compared with the cisplatin control group (all P<0.05), while the serum Cr and BUN levels on the 6th day and the whole-blood platinum levels in the high-dose GMDTC group decreased (all P<0.05). The urinary platinum levels of rats in the three GMDTC dose groups increased on the 1st day after GMDTC administration (all P<0.05), but decreased on the 3rd day compared with the cisplatin control group (all P<0.05). The counts of white blood cells, neutrophils, lymphocytes and platelets of rats in the cisplatin control group were lower than those in the model control group (all P<0.05). There was no significant difference in the above indexes of rats between the three GMDTC dose groups and the cisplatin control group (all P>0.05). Conclusion Intravenous administration of GMDTC at doses of 54 or 108 mg/kg body mass effectively reduce the nephrotoxicity of cisplatin-treated rats with LLC-WRC-256 tumors without affecting the antitumor effect of cisplatin.

ObjectiveTo investigate the protective effect of N-(2R,3R,4R,5R,6R-pentahydroxyhexyl)-(N-disubstituted sodium formate)-L-methylthio-glutamate sodium (GMDTC) against cisplatin-induced acute kidney injury (AKI) in rats. Methods Specific pathogen free male adult SD rats were randomly divided into the control group, model group, low-dose group and high-dose group, with eight rats in each group. The rats in the latter three groups were injected with cisplatin at a dose of 4 mg/kg body mass through the tail vein to establish an AKI model, while the control group was not treated. Rats in the low-dose and high-dose groups were injected with injectable GMDTC at doses of 108 and 433 mg/kg body mass through the tail vein, respectively, in two hours after intoxication, while the rats in the model group were injected with an equal volume of 0.9% sodium chloride solution, once per day for five consecutive days. The 24-hours urine platinum level at day 1, 3, 5 and the level of whole blood platinum, serum platinum, urinary platinum and renal platinum at day 6 were determined using the inductively coupled plasma-mass spectrometry after GMDTC administration. Serum renal functional indicators and electrolyte level were detected, and renal histopathology was observed at day 6 after GMDTC administration. Results The levels of serum urea, serum creatinine, serum calcium ion, whole blood platinum, serum platinum and renal platinum, and the score of renal tubular injury in the model group were higher than those in the control group (all P<0.05). The 24-hours urinary platinum level at day 1, 3 and 5 after GMDTC administration in the model group was also higher than those in the control group (all P<0.05), and AKI changes were observed in histopathology. The levels of serum urea, serum creatinine, serum calcium ion, whole blood platinum, serum platinum, renal platinum, and renal tubular injury scores of rats in the low- and high-dose groups decreased compared with that in the model group (all P<0.05). The 24-hour urinary platinum levels on the first day after GMDTC administration of rats in the low- and high-dose groups increased compared with that in the model group (all P<0.05), as well as the renal histopathological changes of AKI were improved. However, there was no significant difference in the above-mentioned indicators between the low- and high-dose groups (all P>0.05). Conclusion GMDTC can promote the elimination of platinum in urine, effectively reduce the platinum level in blood and renal tissues, alleviate the pathological damage of renal tubules in rats, and improve the cisplatin-induced AKI.

Procurement constitutes a cornerstone of daily operations in public hospitals,involving medical equipment,medical materials,pharmaceuticals,infrastructure projects,office supplies,and service-oriented projects.The responsibility for procurement used to rest on various functional departments overseeing business management,a situation that often led to a lack of transparency and standardization due to decisions made by a single department or a few key cadres.To standardize procurement practices,the national policy has introduced a"procurement"and"management"separation model.In public hospitals,pro-curement includes two main aspects:"procurement"entails the actual execution of purchasing activities,including market re-search,price negotiation,tender document formulation,and contract signing;and"management"involves the preliminary re-search,budgeting and project initiation,installation and commissioning,inventory acceptance,maintenance quality control,and usage management of procured items.The separation of"procurement"and"management"is an important part of the procure-ment management unit in the modern hospital administration.This process-based division ensures the functional distinction be-tween procurement and management,fostering interdepartmental collaboration and mutual oversight,thereby mitigating procure-ment integrity while safeguarding procurement quality.

Objective To investigate the initial dose and safety of intravenous infusion of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) for the displacement of cadmium. Methodsi) Efficacy test. The New Zealand male rabbits were randomly divided into model group, calcium disodium edetate (EDTA) group and GMDTC low-, medium- and high-dose groups after cadmium poisoning using 2.5 cadmium chloride dihydrate. Rabbits in EDTA group were intravenously injected with EDTA dipotassium at a dose of 93.5 mg/kg body weight, rabbits in the three doses groups were intravenously injected of GMDTC at doses of 12.0, 36.0, and 108.0 mg/kg body weight, respectively. The rabbits in the control group (separate set) and model group were intravenously injected with equal volumes of 0.9% sodium chloride solution, administered for five consecutive days per week for 1, 2, and 4 weeks. ii) Toxicity test. Specific pathogen free SD rats were randomly divided into solvent control group and low-, medium- and high-dose groups. In the acute toxicity test, the rats in the three-dose groups were intravenously injected of GMDTC at doses of 200.0, 800.0 and 3 000.0 mg/kg body weight, respectively. In the long-term toxicity test, the rats in the three-dose groups were intravenously injected GMDTC at doses of 100.0, 500.0 and 2 000.0 mg/kg body weight, respectively, once a day for four consecutive weeks, with a recovery period of four weeks. The rats in the solvent control group were given an equal volume 0.9% sodium chloride solution intravenously at the same time. The maximum tolerated dose (MTD) and no observable adverse effect level (NOAEL) were detected. Resultsi) In the one week treatment experiment, the 24 hours urinary cadmium levels of rabbits in the three doses groups were higher than those in the model group at the same time point (all P<0.05). In the two weeks treatment experiment, the 24 hours urinary cadmium levels of rabbits in medium-dose and high-dose groups at the three time points were higher than those in the model group at the same time point (all P<0.05). In the four weeks treatment experiment, the 24 hours urinary cadmium level on the 19th day of rabbits in the low-dose group was higher than that in the model group at the same time point (P<0.05), and the 24 hours urinary cadmium levels of rabbits in medium- and high-dose groups at the five time points were higher than those in the model group at the same time point (all P<0.05), except for the rabbits of fifth day of the medium-dose group. The kidney cadmium levels of rabbits in the low-dose group after four week of treatment and in the medium- and high-dose groups after one, two, and four weeks of treatment decreased compared with the model group (all P<0.05). No obvious adverse effects were observed during the treatment. ii) The MTD of GMDTC in rats administered intravenously in a single dose was 3 000.0 mg/kg body weight. During the period of intravenous infuseion with GMDTC for four consecutive weeks, the blood drug level reached the peak at the end of the first and last administrations (eight min), and no clinical adverse reactions were observed during this period of time, nor was there any apparent accumulation. The NOAEL for intravenous infusion of GMDTC for four consecutive weeks in rats was 500.0 mg/kg body weight. Conclusion The initial dose of the GMDTC injection in the cadmium poisoning rabbit was 36.0 mg/kg body weight, and the recommended initial dose for human is 480.0 mg/person. Intravenous infusion of GMDTC is characterized by rapid absorption, rapid elimination, and no accumulation.

Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Objective To investigate the role of high-mobility group AT-hook 2(HMGA2)in osteogenic differentiation of adipose-derived mesenchymal stem cells(ADSCs)and the effect of Hmga2 knockdown for promoting bone defect repair.Methods Bioinformatics studies using the GEO database and Rstudio software identified HMGA2 as a key factor in adipogenic-osteogenic differentiation balance of ADSCs.The protein-protein interaction network of HMGA2 in osteogenic differentiation was mapped using String and visualized with Cytoscape to predict the downstream targets of HMGA2.Primary mouse ADSCs(mADSCs)were transfected with Hmga2 siRNA,and the changes in osteogenic differentiation of the cells were evaluated using alkaline phosphatase staining and Alizarin red S staining.The expressions of osteogenic markers Runt-related transcription factor 2(RUNX2),osteopontin(OPN),and osteocalcein(OCN)in the transfected cells were detected using RT-qPCR and Western blotting.In a mouse model of critical-sized calvarial defects,mADSCs with Hmga2-knockdown were transplanted into the defect,and bone repair was evaluated 6 weeks later using micro-CT scanning and histological staining.Results GEO database analysis showed that HMGA2 expression was upregulated during adipogenic differentiation of ADSCs.Protein-protein interaction network analysis suggested that the potential HMGA2 targets in osteogenic differentiation of ADSCs included SMAD7,CDH1,CDH2,SNAI1,SMAD9,IGF2BP3,and ALDH1A1.In mADSCs,Hmga2 knockdown significantly upregulated the expressions of RUNX2,OPN,and OCN and increased cellular alkaline phosphatase activity and calcium deposition.In a critical-sized calvarial defect model,transplantation of mADSCs with Hmga2 knockdown significantly promoted new bone formation.Conclusion HMGA2 is a crucial regulator of osteogenic differentiation in ADSCs,and Hmga2 knockdown significantly promotes osteogenic differentiation of ADSCs and accelerates ADSCs-mediated bone defect repair in mice.

Objective:To study the characteristics and influencing factors of coping styles of clinical ophthalmic interns under psychological stress, so as to provide scientific basis for promoting the mental health development of medical students.Methods:In 2019, 103 students of Sun Yat-sen University who participated in clinical practice of ophthalmology were investigated by cluster sampling with general situation questionnaire and simple coping style questionnaire. The database was established by Epidata, and the data was statistically analyzed by SPSS 25.0 software.Results:The scores of positive coping and negative coping were (1.70±0.10) and (1.30±0.05) respectively, which were all lower than the norm ( P < 0.001). The scores of non first time practice students were 0.087 points higher than those of first time practice students; the scores of eight-year students were 0.124 points higher than those of five-year students; the scores of positive coping increased by 0.015 points for each level of family income increase. Men scored 0.027 points higher than women in negative coping scores; eight-year students scored 0.053 points lower than five-year students in negative coping scores; family income increased by one grade, negative coping scores decreased by 0.017 points; rural registered residence students scored 0.035 points higher than urban registered residence students in negative coping scores; non first practice students scored 0.074 points higher than the first practice students in negative coping scores. Conclusion:Educators should pay close attention to the coping styles of clinical ophthalmic interns, carry out mental health education and guidance of coping methods according to the characteristics of different groups, take effective measures to improve students' stress coping ability and promote the smooth development of clinical practice in ophthalmology.

Objective     To investigate the influence of prior percutaneous coronary intervention (PCI) on the outcome of coronary artery bypass grafting (CABG). Methods     Clinical data of 5 216 patients from Jiangsu Province CABG registry who underwent primary isolated CABG from 2016 to 2019 were retrospectively analyzed. Patients were divided into a PCI group (n=673) and a non-PCI group (n=4 543) according to whether they had received PCI treatment. The PCI group included 491 males and 182 females, aged 62.6±8.2 years, and the non-PCI group included 3 335 males and 1 208 females, aged 63.7±8.7 years. Multivariable logistic regression and propensity score matching (PSM) were used to compare 30-day mortality, incidence of major complications and 1-year follow-up outcomes between the two groups. Results     Both in original cohort and matched cohort, there was no statistical difference in the 30-day mortality [14 (2.1%) vs. 77 (1.7%), P=0.579; 14 (2.1%) vs. 11 (1.6%), P=0.686], or the incidence of major complications (myocardial infarction, stroke, mechanical ventilation≥24 h, dialysis for new-onset renal failure, deep sternal wound infection and atrial fibrillation) (all P>0.05). The rate of reoperation for bleeding in the PCI group was higher than that in the non-PCI group [19 (2.8%) vs. 67 (1.5%), P=0.016; 19 (2.8%) vs. 7 (1.0%), P=0.029]. Both in original cohort and matched cohort, there was no statistical difference in 1-year survival rate between the two groups [613 (93.1%) vs. 4 225 (94.6%), P=0.119; 613 (93.1%) vs. 630 (95.2%), P=0.124], while the re-admission rate in the PCI group was significantly higher than that in the non-PCI group [32 (4.9%) vs. 113 (2.5%), P=0.001; 32 (4.9%) vs. 17 (2.6%), P=0.040]. Conclusion     This study shows that a history of PCI treatment does not significantly increase the perioperative mortality and major complications of CABG, but increases the rate of cardiogenic re-admission 1 year postoperatively.

BACKGROUND: Non-transport unintentional injuries (NTUIs) are major public concerns, especially among children and adolescents in low- and middle-income countries. With environmental and cognitive changes, a recent systematic description of global trends and regional differences concerning NTUIs is urgently needed for the global agenda of relevant policy-making and intervention target findings. METHODS: We used mortality, population, and socio-demographic-index (SDI) data from Global Burden of Disease 2019 to analyze the trends of NTUIs mortality. We applied the slope index of inequality (SII) and relative index of inequality (RII) to measure the absolute and relative inequality between countries and territories. The concentration curve and concentration index (CI) were also used to measure the inequality. We conducted a sensitivity analysis to make our findings credible. RESULTS: In 2019, there were 205,000 deaths due to NTUIs among children and adolescents aged 5 to 24 years, which decreased from 375,000 in 1990. In 2019, the age-standardized mortality rate (ASMR) was 8.13 per 100,000, ranging from the lowest in the Netherlands (0.90 per 100,000) to the highest in the Solomon Islands (29.34 per 100,000). The low-middle SDI group had the highest ASMR of NTUIs, while the low SDI group had the slowest decrease. After excluding the death caused by "exposure to forces of nature" and "other unintentional injuries", drowning accounted for the most deaths in almost every SDI group, gender, and age group, but the major causes of death varied in different subgroups. For example, animal contact was a major cause in low and low-middle SDI groups but less in high SDI groups, while high and high-middle SDI groups had a higher proportion of deaths for foreign body and poisonings. The SII showed a declining trend, but the RII and CI did not, which might indicate that inequality was persistent. Similar results were found in the sensitivity analysis. CONCLUSIONS Despite the declining trend of the mortality rate and the narrowing gap between countries, there were still a large number of children and adolescents dying from NTUIs, and those experiencing social-economic disadvantages remained at high mortality. Embedding the prevention of NTUIs into sustainable development goals might contribute to the progress of reducing death and inequalities, which ensures that no one is left behind.
Global Burden of Disease

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome