Objective Fasting hypometabolism regulation technology has broad application potential in long-term space flight and survival in extreme extraterrestrial environments.In-depth research on the substrate conversion of energy metabolism and the formation of new steady states under fasting hypometabolism will provide theoretical basis and experimental data support for formulating effective prolonged fasting application mode.Methods 30 SD rats were randomly divided into control group and fasting group(fasting for 1,2,3,and 5 days).Blood biochemical examination,qRT-PCR,and western blotting were performed to analyze the body weight,blood biochemistry,and expression changes of genes and proteins related to glucose and lipid metabolism during different fasting periods.Results Prolonged fasting significantly reduced the body weight,blood glucose,and triglyceride levels of rats;increased the blood ketone level,and replaced glucose as the main energy substance in the body.There are temporal and tissue-specific changes as a whole.Hepatic and renal gluconeogenesis play major roles respectively during different fasting periods.As the fasting time prolongs,the level of hepatic gluconeogenesis gradually decreases,the content of FFA in the blood increases,the expression level of genes related to fat synthesis decreases,fatty acid oxidation is enhanced,and the expression level of the key gene HMGCS2 for ketone body generation increases.Conclusion During prolonged fasting,there is a significant conversion of glucose-ketone energy supply substrates,and a new steady state of energy metabolism mainly supplied by ketone bodies is formed within 2-5 days of fasting.The body maintains a low metabolic state by regulating changes in key genes in pathways such as glucose and lipid metabolism.

Objective To explore the correlation of complex inflammation indexes,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)with the severity of acute ische-mic stroke(AIS).Methods A total of 278 patients with brain MRI-confirmed AIS admitted in our department between March 2018 and September 2023 were enrolled retrospectively,and according to the National Institutes of Health Stroke Scale(NIHSS)score at admission,they were divided into a mild stroke group(NIHSS score≤3,n=157)and a moderate-severe stroke group(NIHSS score＞3,n=121).Clinical data and results of laboratory tests at admission were collec-ted,and NLR and PLR were calculated.Multivariate logistic regression analysis was performed to assess the association of NLR and PLR with AIS severity.Results Compared with the mild stroke group,the moderate-severe stroke group had significantly older age,larger proportions of atrial fibrillation and pre-morbid Modified Rankin Scale(mRS)score＞1,higher NLR and PLR,and higher ratio of culprit large vessel stenosis,and a lower rate of transient ischemic attack(TIA)(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that TIA(95％CI:0.017-0.455,P=0.004)was a protective factor,and pre-morbid mRS＞1(95％CI:1.451-6.700,P=0.004),NLR(95％CI:1.041-1.346,P=0.010)and culprit large vessel stenosis(95％CI:1.370-4.415,P=0.003)were risk factors for the severity of AIS.Conclusion Inflammation is involved in the pathogenesis of AIS,and the complex inflammatory index,NLR may be an inde-pendent risk factor for the severity of AIS.

Objective:To investigate the clinical efficacy and safety of ultrasound-guided thyroid injection of dexamethasone in the treatment of subacute thyroiditis (SAT).Methods:This is a randomized controlled study involving 32 patients with SAT who received treatment at Endocrinology Clinic of Heilongjiang Provincial Hospital between June 2022 and March 2023. The patients were randomly divided into an observation group and a control group ( n = 16 per group) using a random number table method. The observation group received ultrasound-guided injection of dexamethasone (5 mg per injection, once a week) into the thyroid lesion, while the control group was treated with oral prednisone acetate tablets (5 mg per dose, three times a day). Both groups were treated for 4 weeks. The clinical efficacy, time taken for body temperature to return to normal, time for pain resolution, time for goiter regression, time for thyroid function to normalize, as well as recurrence rates and adverse reactions, were compared between the two groups. Results:The response rate in the observation group was 100% (16/16), which was significantly higher than that in the control group [75% (12/16), χ2 = 4.57, P = 0.033]. The time taken for body temperature to return to normal, the time for goiter regression, and the time for goiter regression in the observation group were (3.5 ± 3.6) days, (7.4 ± 2.5) days, and (11.6 ± 7.4) days, respectively, which were significantly shorter than those in the control group [(6.1 ± 3.2) days, (9.9 ± 3.5) days, (16.9 ± 6.8) days, t = -2.16, -2.33, -2.11, all P < 0.05]. After 4 weeks of treatment, the observation group showed significantly lower body mass index, fasting blood glucose, and serum triglyceride levels compared to the control group ( t = -2.07, -2.46, -2.13, all P < 0.05). The recurrence rate in the observation group was 0%, which was significantly lower than that in the control group [25% (4/16), χ2 = 4.57, P = 0.033]. Conclusions:The efficacy and safety of ultrasound-guided local thyroid injection of dexamethasone for the treatment of SAT are superior to those of the oral treatment regimen.

Objective:To investigate the clinical efficacy and safety of ultrasound-guided thyroid injection of dexamethasone in the treatment of subacute thyroiditis (SAT).Methods:This is a randomized controlled study involving 32 patients with SAT who received treatment at Endocrinology Clinic of Heilongjiang Provincial Hospital between June 2022 and March 2023. The patients were randomly divided into an observation group and a control group ( n = 16 per group) using a random number table method. The observation group received ultrasound-guided injection of dexamethasone (5 mg per injection, once a week) into the thyroid lesion, while the control group was treated with oral prednisone acetate tablets (5 mg per dose, three times a day). Both groups were treated for 4 weeks. The clinical efficacy, time taken for body temperature to return to normal, time for pain resolution, time for goiter regression, time for thyroid function to normalize, as well as recurrence rates and adverse reactions, were compared between the two groups. Results:The response rate in the observation group was 100% (16/16), which was significantly higher than that in the control group [75% (12/16), χ2 = 4.57, P = 0.033]. The time taken for body temperature to return to normal, the time for goiter regression, and the time for goiter regression in the observation group were (3.5 ± 3.6) days, (7.4 ± 2.5) days, and (11.6 ± 7.4) days, respectively, which were significantly shorter than those in the control group [(6.1 ± 3.2) days, (9.9 ± 3.5) days, (16.9 ± 6.8) days, t = -2.16, -2.33, -2.11, all P < 0.05]. After 4 weeks of treatment, the observation group showed significantly lower body mass index, fasting blood glucose, and serum triglyceride levels compared to the control group ( t = -2.07, -2.46, -2.13, all P < 0.05). The recurrence rate in the observation group was 0%, which was significantly lower than that in the control group [25% (4/16), χ2 = 4.57, P = 0.033]. Conclusions:The efficacy and safety of ultrasound-guided local thyroid injection of dexamethasone for the treatment of SAT are superior to those of the oral treatment regimen.

Objective To explore the correlation of complex inflammation indexes,neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)with the severity of acute ische-mic stroke(AIS).Methods A total of 278 patients with brain MRI-confirmed AIS admitted in our department between March 2018 and September 2023 were enrolled retrospectively,and according to the National Institutes of Health Stroke Scale(NIHSS)score at admission,they were divided into a mild stroke group(NIHSS score≤3,n=157)and a moderate-severe stroke group(NIHSS score＞3,n=121).Clinical data and results of laboratory tests at admission were collec-ted,and NLR and PLR were calculated.Multivariate logistic regression analysis was performed to assess the association of NLR and PLR with AIS severity.Results Compared with the mild stroke group,the moderate-severe stroke group had significantly older age,larger proportions of atrial fibrillation and pre-morbid Modified Rankin Scale(mRS)score＞1,higher NLR and PLR,and higher ratio of culprit large vessel stenosis,and a lower rate of transient ischemic attack(TIA)(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that TIA(95％CI:0.017-0.455,P=0.004)was a protective factor,and pre-morbid mRS＞1(95％CI:1.451-6.700,P=0.004),NLR(95％CI:1.041-1.346,P=0.010)and culprit large vessel stenosis(95％CI:1.370-4.415,P=0.003)were risk factors for the severity of AIS.Conclusion Inflammation is involved in the pathogenesis of AIS,and the complex inflammatory index,NLR may be an inde-pendent risk factor for the severity of AIS.

Objective:To investigate the regulatory role of miR-17-5p on B7-H3 and its immunomodulatory role in the develop-ment of colorectal cancer.Methods:Twenty-five pairs of human colorectal cancer tissues and adjacent normal tissues were collected,and the expression levels of miR-17-5p,B7-H3 and PD-L1 were analyzed by real-time fluorescence quantitative PCR,protein immuno-blotting and immunohistochemical assays.Human colorectal cancer HCT-116 cells were divided into four groups:miR-NC group,miR-17-5p mimic group,si-NC group and si-B7-H3 group.The growth,invasive ability and apoptosis rate of HCT-116 cells were ana-lyzed by cell colony formation assay,Transwell assay and flow cytometry.The regulatory effect of miR-17-5p on B7-H3 was analyzed by luciferase reporter gene assay.The levels of IL-2,IL-4,IL-6,IL-10,IFN-γ and TNF-α cytokines in the cell culture medium were analyzed by ELISA.Results:Compared with paracancerous tissues,miR-17-5p expression was decreased and B7-H3 expression was increased in colorectal cancer tissues.miR-17-5p mimic and si-B7-H3 were able to reduce the number of HCT-116 cell colony forma-tion and invasion,promote HCT-116 cell apoptosis,and decrease the levels of IL-2,IL-4,IL-6,IL-10,IFN-γ and TNF-α cytokines in culture medium.In addition,miR-17-5p mimic and si B7-H3 were able to inhibit PD-L1 expression in HCT-116 cells.Conclusion:miR-17-5p can targeting inhibit B7-H3 expression,affect the immunomodulatory role in colorectal cancer development,and inhibit metastasis and promote apoptosis of colorectal cancer cells.

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.

As d-amino acids play important roles in the physiological metabolism of bacteria, combination of d-amino acids with antibiotics may provide synergistic antibacterial activity. The aim of the study was to evaluate and activity of d-serine alone and in combination with -lactams against methicillin-resistant (MRSA) strains, and to explore the possible sensitization mechanisms. The activity of d-serine, -lactams alone and in combinations was evaluated both by standard MICs, time-kill curves and checkerboard assays, and by murine systemic infection model as well as neutropenic thigh infection model. An synergistic effect was demonstrated with the combination of d-serine and -lactams against MRSA standard and clinical strains. Importantly, the combinations enhanced the therapeutic efficacy in the animal models as compared to -lactam alone groups. Initial mechanism study suggested possible revision of d-alanine-d-alanine residue to d-alanine-d-serine in peptidoglycan by adding of d-alanine in the medium, which may cause decreased affinity to PBPs during transpeptidation. In conclusion, d-serine had synergistic activity in combination with -lactams against MRSA strains both and . Considering the relatively good safety of d-serine alone or in combination with -lactams, d-serine is worth following up as new anti-MRSA infection strategies.

The objective of this study was to investigate the genetic basis of high level aminoglycoside resistance in Acinetobacter baumannii clinical isolates from Beijing, China. 173 A. baumannii clinical isolates from hospitals in Beijing from 2006 to 2009 were first subjected to high level aminoglycoside resistance (HLAR, MIC to gentamicin and amikacin>512 µg/mL) phenotype selection by broth microdilution method. The strains were then subjected to genetic basis analysis by PCR detection of the aminoglycoside modifying enzyme genes (aac(3)-I, aac(3)-IIc, aac(6')-Ib, aac(6')-II, aph(4)-Ia, aph(3')-I, aph(3')-IIb, aph(3')-IIIa, aph(3')-VIa, aph(2″)-Ib, aph(2″)-Ic, aph(2″)-Id, ant(2″)-Ia, ant(3″)-I and ant(4')-Ia) and the 16S rRNA methylase genes (armA, rmtB and rmtC). Correlation analysis between the presence of aminoglycoside resistance gene and HLAR phenotype were performed by SPSS. Totally 102 (58.96%) HLAR isolates were selected. The HLAR rates for year 2006, 2007, 2008 and 2009 were 52.63%, 65.22%, 51.11% and 70.83%, respectively. Five modifying enzyme genes (aac(3)-I, detection rate of 65.69%; aac(6')-Ib, detection rate of 45.10%; aph(3')-I, detection rate of 47.06%; aph(3')-IIb, detection rate of 0.98%; ant(3″)-I, detection rate of 95.10%) and one methylase gene (armA, detection rate of 98.04%) were detected in the 102 A. baumannii with aac(3)-I+aac(6')-Ib+ant(3″)-I+armA (detection rate of 25.49%), aac(3)-I+aph(3')-I+ant(3″)-I+armA (detection rate of 21.57%) and ant(3″)-I+armA (detection rate of 12.75%) being the most prevalent gene profiles. The values of chi-square tests showed correlation of armA, ant(3″)-I, aac(3)-I, aph(3')-I and aac(6')-Ib with HLAR. armA had significant correlation (contingency coefficient 0.685) and good contingency with HLAR (kappa 0.940). The high rates of HLAR may cause a serious problem for combination therapy of aminoglycoside with β-lactams against A. baumannii infections. As armA was reported to be able to cause high level aminoglycoside resistance to most of the clinical important aminoglycosides (gentamicin, amikacin, tobramycin, etc), the function of aminoglycoside modifying enzyme gene(s) in A. baumannii carrying armA deserves further investigation.

Objective To study the change and the correlation of serum soluble vascular cell adhesion molecuh-1(sVCAM-1)level with diabetic retinopathy in type 2 diabetic patients.Methods 60 type 2 diabetic patients were selected for the study through the examination of ophthalmoscope and/or fundus fluorescence angiography by ophthalmologist.Diabetic patients were divided into three main groups:No signs of diabetic retinopathy(NDR)(n=20);Background DR(BDR)(n=20)Proliferative DR(PDR)(n=20).Healthy individuals matching sex and age of the patients were used as controls(n=20);Serum sVCAM-1 level was measured by ELISA,compared in diabetes without DR,with BDR,with PDR.These levels were compared with those of 20 controls.Results The serum level of sVCAM-1 in the DM patients with PDR or BDR and those without DR were significantly higher than those in healthy controls(all P＜0.001);Serum level of sVCAM-1 in PDR groups were higherthan those in DM patients with BDR or patients without DR(all P＜0.001);There was no difference between the patients with BDR and those without DR (P＞0.05).(4)In the DM patients,there was a positive correlation between serum sVCAM-1 and the course of diseases(r=0.338,P＜0.05),but no relationship with HbA1C,FBG,CHO,TG,LDL and INS.Conclusion Increased serum level of sVCAM-1 in different stage of DR patients suggested that they hagbe play an important role in the development of DR,and may assess the severity of diabetic retinopathy.The measuremem of serum sVCAM-1 levels in type 2 diabetic patients could be clinically useful for early diagnosis or treatment of diabetic retinopathy.