Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

Objective:To investigate the efficacy of dapagliflozin combined with tirofiban in patients with type 2 diabetes mellitus complicated with coronary heart disease.Methods:A total of 120 patients with type 2 diabetes mellitus and coronary heart disease treated in Fuyang People′s Hospital from January to August 2022 were prospectively selected as subjects. According to different treatment methods, they were divided into control group and experimental group. The control group was treated with tirofiban, and the experimental group was treated with dapagliflozin combined with tirofiban. The efficacy and safety of treatments between the two groups were compared.Results:After 3 months of treatment, fasting plasma glucose (FPG), 2 h postprandional blood glucose (2 h PG), glycated hemoglobin (HbA 1c), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), D-dimer (D-D) and fibrinogen (FIB) levels in 2 groups were decreased compared with before treatment:experimental group: (7.33 ± 1.77) mmol/L vs. (9.45 ± 2.05) mmol/L, (10.33 ± 2.07) mmol/L vs. (13.57 ± 2.88) mmol/L, (7.22 ± 1.28) % vs. (9.25 ± 1.78) %, (1.98 ± 0.29) mmol/L vs. (6.05 ± 1.24) mmol/L, (2.95 ± 0.37) mmol/L vs. (4.35 ± 0.76) mmol/L, (0.78 ± 0.23) mg/L vs. (1.85 ± 0.79) mg/L, (2.57 ± 0.37) g/L vs. (7.15 ± 1.36) g/L, control group: (8.21 ± 1.85) mmol/L vs. (9.68 ± 2.17) mmol/L, (11.78 ± 2.26) mmol/L vs. (13.89 ± 3.02) mmol/L, (8.25 ± 1.36) % vs. (9.37 ± 1.86) %, (2.77 ± 0.42) mmol/L vs. (6.08 ± 1.22) mmol/L, (3.84 ± 0.44) mmol/L vs. (4.27 ± 0.72) mmol/L, (1.34 ± 0.52) mg/L vs. (1.81 ± 0.72) mg/L, (5.25 ± 0.84 ) g/L vs. (7.11 ± 1.28) g/L, the differences were statistically significant ( P< 0.05). The levels of FPG, 2 h PG, HbA 1c, TC, LDL-C, D-D and FIB between the two groups were statistically significant ( P<0.05). High density lipoprotein cholesterol (HDL-C) level, left ventricular ejection fraction (LVEF), cardiac blood transfusion volume (CO), stroke output (SV), thrombin time (TT) and partially activated prothrombin time (APTT) were all increased: experimental group: (1.76 ± 0.30) mmol/L vs. (1.07 ± 0.28) mmol/L, (68.64 ± 12.91) % vs. (45.05 ± 12.24) %, (4.88 ± 0.91) L/min vs. (3.95 ± 1.12) L/min, (53.66 ± 5.43) ml/min vs. (43.27 ± 4.88) ml/min, (31.83 ± 4.39) s vs. (23.25 ± 3.44) s, (13.85 ± 2.17) s vs. (10.75 ± 1.56) s, control group: (1.43 ± 0.26) mmol/L vs. (1.06 ± 0.24) mmol/L, (60.37 ± 11.86) % vs. (45.42 ± 12.41) %, (4.37 ± 0.84) L/min vs. (4.17 ± 1.16) L/min, (47.86 ± 5.27) ml/min vs. (43.36 ± 4.94) ml/min, (27.24 ± 3.91) s vs. (23.78 ± 3.62) s, (12.74 ± 1.94) s vs. (10.89 ± 1.78) s, the differences were statistically significant ( P<0.05). There were significant differences in HDL-C, LVEF, CO, SV, TT and APTT between the two groups ( P<0.05). The incidence of adverse reactions in experimental group was lower than that in control group during treatment: 5.00% (3/60) vs. 16.67% (10/60), and the difference was statistically significant ( P<0.05). Conclusions:Dapagliflozin combined with tirofiban in the treatment of patients with type 2 diabetes mellitus complicated with coronary heart disease has obvious curative effect, and can improve blood glucose and blood lipid levels, coagulation function and cardiac function, with high safety.

Background::The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee–CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association.Methods::A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data ( n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. Results::Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed ( P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee–CKD association. Conclusions::In addition to the overall inverse coffee–CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.

Objective:To understand the current situation of syphilis infection among 12 295 blood donors in Huainan area, so as to provide reference for the management of public health.Methods:The Treponema pallidum(TP) antibody of the blood donors was screened by enzyme-linked immunosorbent assay, and the unqualified blood donors for TP antibody were confirmed by Treponema pallidum particle agglutination(TPPA).Results:There were 48 blood donors TPPA positive among 12 295 blood donors in Huainan area, and the TPPA positive rate was 3.90‰(48/12 295). There was no statistically significant difference in the TPPA positive rate of the different gender blood donors[male 3.12‰(22/7 048) vs.female 4.96‰(26/5 247)] in Huainan area( u=1.61, P>0.05). There was statistically significant difference in the TPPA positive rate of the different marriage blood donors[married 5.33‰(42/7 884) vs.unmarried 2.01‰(6/2 989)] in Huainan area( u=2.33, P<0.05). There was statistically significant difference in the TPPA positive rate of the blood donors among different education level in Huainan area(χ 2=29.94, P<0.05). There was no statistically significant difference in the TPPA positive rate of the blood donors among ABO blood groups in Huainan area(χ 2=2.24, P>0.05). Conclusion:There are significant differences in the TPPA positive rates of the blood donors among marital status and education level in Huainan area.

OBJECTIVE: Patients with chronic neuropathic pain (CNP) have a higher incidence to develop depression. However, its pathogenesis has not yet been fully elucidated. Here we aimed to investigate the role of inflammatory cytokines in CNP-related anhedonia, which is a core symptom of depression, and to explore the effects of ketamine and parecoxib on pain and anhedonia. METHODS: A rat model of spared nerve injury (SNI) was constructed to mimic CNP. Hierarchical cluster analysis of sucrose preference test (SPT) was applied to classify the SNI rats into anhedonia susceptible and unsusceptible. Inflammatory cytokines in medial prefrontal cortex (mPFC) of brain, serum and L2–5 spinal cord were measured. Moreover, effects of ketamine or parecoxib on mechanical withdrawal test (MWT) and SPT in anhedonia susceptible rats were detected. RESULTS: Tumor necrosis factor (TNF)-α was increased in mPFC, serum and and spinal cord of anhedonia susceptible rats. Furthermore, anhedonia susceptible and unsusceptible rats both increased the interleukin (IL)-1β level in mPFC, serum and spinal cord. IL-6 was altered in serum and spinal cord, but not in mPFC. IL-10 was significantly altered in mPFC and serum, but not in spinal cord. Additionally, ketamine treatment significantly attenuated the decreased results of MWT and SPT in anhedonia susceptible rats, and that parecoxib significantly improved the MWT score, but failed to alter the result of SPT. CONCLUSION: These findings suggest that abnormalities in inflammatory cytokines confer susceptible to anhedonia in a rat model of SNI. Ketamine, a fast-acting antidepressant, has pharmacological benefits to alleviate pain and anhedonia symptoms.
Anhedonia ; Animals ; Brain ; Cytokines ; Depression ; Humans ; Incidence ; Interleukin-10 ; Interleukin-6 ; Interleukins ; Ketamine ; Models, Animal ; Neuralgia ; Neurogenic Inflammation ; Prefrontal Cortex ; Rats ; Spinal Cord ; Sucrose ; Tumor Necrosis Factor-alpha

Aim To investigate the effect of sphingo-sine kinase 1 (SphK1 )on unilateral ureteral obstruc-tion(UUO)-induced tubulointerstitial fibrosis and ex-plore the possible mechanism.Methods The CD-1 mice were randomly divided into four groups:sham-op-eration group(Sham),PF-543 treatment control group (Sham +PF-543),model group(UUO)and PF-543 treatment group(UUO +PF-543).On 1 ,3,7 and 1 4 d after operation,eight mice were selected randomly from each group and sacrificed.The protein expressions of SphK1 ,mature TGF-β1 ,FN,ColⅠ,LC3,Beclin1 ,Atg5 and Atg1 2 were observed by Western blot.The histo-logical changes were examined by Masson′s trichrome stain.Immunhistochemistry was performed to measure the levels of expression of SphK1 ,FN and Col Ⅰ. Transmission electron microscope was used to observe the autophagic body.Results SphK1 expression and autophagy were both upregulated in a mouse model of kidney fibrosis induced by UUO. Meanwhile, in-creased mature TGF-β1 and deposition of extracellular matrix(ECM)were observed in tubulointerstitial areas compared with sham-operated mice.After intraperito-neal injection with the SphK1 specific inhibitor PF-543 in UUO mice,enhanced expression of SphK1 and acti-vated autophagy were significantly abrogated.Howev-er,aggravation of renal fibrosis was detected when SphK1 inhibitor PF-543 was applied to suppress SphK1 expression in UUO mice.Conclusion SphK1 activa-tion is renoprotective through the induction of autoph-agy in the pathogenesis of kidney fibrosis.

Objective: To explore the relationship between fathers′ nursing time and maternal parenting stress of children with autism spectrum disorder(ASD). Method: Mothers of 98 ASD children who were first diagnosed in the department of Child Health Care, Children′s Hospital of Fudan University during June 2015 to January 2016 were included in the ASD group, with mothers of 92 typical children from a Community Maternal and Child Health Hospital and a kindergarten in the control group. The evaluation of parenting stress, parents′ nursing time and other related factors were cross-sectionally analyzed. Interview was conducted with the following tools: Parental Stress Index-Short Form(PSI-SF)for maternal parenting stress, and self-made General Parenting Information Questionnaire for nursing time of both parents and other related factors. The relationships were analyzed by Multiple Linear Regression analysis and Wilcoxon Rank-Sum test. Result: Maternal parenting stress of ASD children had a significant negative correlation with father′s nursing time in total score of parenting stress, PCDI domain and PD domain (t=-2.76, -2.98, -2.79; P=0.007, 0.004, 0.006), within which PD domain also included family annual income and mothers′ nursing time (R²=0.22, 0.24, 0.25); while no such correlation was found in control group in terms of father′s nursing time(P=0.22, 0.42, 0.06). Wilcoxon Rank-Sum test showed that in 62 (63.3%) double-income ASD families and 72(78.3%) double-income typical families, there were significant differences between ASD fathers′ and ASD mothers′and typical fathers′nursing time(2.0(0.5, 2.1)vs. 3.5(2.4, 6.0)vs. 3.0(2.0, 4.7)h, t=-86.32、-49.65, all P<0.01). Conclusion Lack of fathers′ involvements was common in ASD children′s families. Increasing these fathers′ nursing time, as well as their enthusiasm and initiative in the family intervention could relieve maternal parenting stress and improve the intervention pattern of ASD children.

Objective To analyze the clinical efficacy of internal rib fixation combined with external chest fixation and mechanical ventilation for traumatic flail chest with pulmonary contusion.Methods Sixty cases of traumatic flail chest with pulmonary contusion treated from January 2011 to December 2014 were assigned to experimental group (30 cases) and control group (30 cases) according to the random number table.Patients in control group received thoracic external fixation combined with mechanical ventilation.In experimental group the patients received the same care but in addition they had rib fixation.The two groups were compared with regard to general condition, arterial blood gas as well as vital signs before treatment and 24 hours after treatment, lung function 3 months after discharge, complication rate and mortality.Results ICU stay [(6.8 ± 1.0) d], hospital stay [(15.0 ± 1.8) d] and duration of mechanical ventilation [(4.8 ± 1.0) d] in experimental group were significantly lower than these in control group [(13.6 ± 2.5) d, (21.4 ± 2.6) d, (10.3 ± 1.3) d, respectively] (P ＜ 0.01).After treatment for 24 hours in either group, the pH value, PaO2, oxygenation index and systolic pressure (SBP) were significantly increased, and partial pressure of carbon dioxide (PaCO2), heart rate (HR) and respiratory rate (RR) were significantly lowered as compared to these before treatment (P ＜0.05).After treatment for 24 hours, experimental group demonstrated significantly enhanced levels in pH value,PaO2, oxygenation index and SBP but lowered levels in PaCO2, HR and RR as compared to control group (P ＜ 0.05).Three months after discharge, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), 75％ forced expiratory flow (FEF75％) and total lung capacity (TLC) in experimental group were (81.7 ±2.6)％, (75.4 ±4.1)％, (83.2 ±4.6)％,(69.1 ±2.3)％, and (88.7 ±3.4)％ respectively, significantly higher than (69.0 ±3.6)％, (71.3 ± 3.9) ％, (78.9 ± 4.3) ％, (62.3 ± 3.3) ％, and (79.0 ± 4.6) ％ respectively in control group (P ＜0.01).In experimental group, there were four cases of pulmonary infection (13％), three pulmonary atelectasis(10％) and one intercostal neuralgia (3％).In control group, there were six cases of pulmonary infection (20％), five pulmonary atelectasis (17％), four intercostal neuralgia (13％) and four thoracocyllosis(13％)(P ＜0.05).There was no significant difference in mortality between the two groups.Conclusion Treatment effect of internal rib fixation for flail chest with pulmonary contusion is improved in combination with mechanical ventilation and external chest fixation.

Objective To evaluate the outcome of reoperation(after I stage anterior/posterior operation)for thoracolumbar fractures combined with kyphosis and spinal cord injury. Methods A retrospective study was done on the medical records of 12 patients who underwent two-stage decompression with kyphosis and neurologic deficit due to single-stage approach(anterior or posterior) operation of thoracolumbar fractures combined with spinal cord injury between January 2005 and April 2009.There were 9 males and 3 females,at mean age of 34.6 years(range,19-57 years).According to the Denis classification,there were five patients with burst fractures,five with compression fractures and two with fracture dislocation.All the patients had couns medullaris injury.Of all the patients,five underwent one stage anterior approach surgery and the others underwent posterior approach operation.All the patients had vailous degrees of neurological symptoms.The patients treated with one stage anterior surgery were treated with two stage posterior surgery and the patients treated with one stage posterior surgery were treated with the two stage anterior operation.The mean interval from one stage operation to two stage decompression was 13.4 months(range,12-18 months).The radiologic,neurologic and functional outcomes were assessed through observation of the Cobb angle,Frankel spinal cord injury grading and Japanese Orthopaedic Association Scores(JOA). Results AIl the patients were followed up for mean 25 months (12-48months),which showed primary healing of the incisions in all the patients.The average anterior and posterior heisht of the vertebrae wers corrected from preoperative 42.6%and 70.5%to postoperative 92.5%and 95.7%and to 87.3%and 92.2%at the final follow-up respectively.Neurologic status was improved at least one Frankel grade in the patients who had preoperative incomplete paraplegia.The Cobb angle was corrected from preoperative 36.3°to postoperative 5.8°and to 5.9°at the final follow-up(P<0.05).No patient had any notable loss of correction between discharge and final follow-up.According to JOA coring,the results were excellent in nine patients,good in two and fair in one,with excellence rate of 92%. Conclusions Two stage decompression for epiconus and cauda equina syndrome resulted from one stage approach(anterior or posterior)operation of thoracolumbar fractures combined with spinal cord injury call attain satisfactory correction of the kyphosis and nerve decompression as well as various degrees of nerve function recovery.

Objective To observe the clinical efficacy of percutaneous vertebroplasty (PVP) with percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fracture(OVCF) by systematic review. Methods From September 2005 to March 2009,46 cases of fresh OVCF were treated. Patients were divided into 2 groups (A, B), according to Jikei grade, Genant semiquantitative method, injury vertebra number. Twenty-five cases(group A)were treated by PVP,8 males and 17 females with the age of 52 - 78 years (average 69). Vertebra segment of fracture was within T6 - L5 (14 in case thoracical vertebrae and 11 lumbar vertebrae). Twenty-one cases(group B)were treated by PKP,There were 6 males and 15 females with the age of 54 - 82 years (average 71). Vertebra segment of fracture was within T6 - L4 (12 in case thoracical vertebrae and 9 lumbar vertebrae). The clinical efficacy, incidence rate of complication, the anterior height of vertebrae body,visual analogue pain scale(VAS) ,ease of pain were measured preoperatively and at 6 weeks, 3 and 6 months and 1 year postoperatively between the two groups. Results All the patients were followed up for 12 -45 months with an average of 23.5 months. The average recovery of anterior height of vertebrae body was respectively(85.95 ± 4.31) % in group A and (93.64 ± 3.35) % in group B,which statistically difference in vertebral height between two groups (P ＜ 0.05). No statistical significant difference was seen in VAS, analgesic durg (AID) and ease of pain complication between two groups (P ＞0. 05). Statistical significant difference was noted in pre-postoperatively between intra-two groups (P ＜0. 05). Conclusions PVP and PKP can quickly relieve pain and enhance vertebral stability in treating thoracolumbar OVCF according to evaluation parameter, and have the similar therapeutic efficacy in treatment of OVCF with minimal invasion. However, PKP is superior in the recovery of vertebral height.