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 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 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.

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.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective:To investigate the expressions and significances of autophagy-related genes Beclin-1, LC3 and p62 in esophageal squamous cell carcinoma (ESCC).Methods:The clinical data of 112 patients with primary ESCC who underwent surgery at the 81st Group Army Hospital of Chinese PLA from January 2015 to December 2016 were retrospectively analyzed. Immunohistochemistry was used to examine the expressions of Beclin-1, p62 and LC3 proteins in 112 ESCC tissues and 31 adjacent normal esophageal mucosa tissues. Furthermore, the expressions of the above three autophagy-related markers in ESCC and the relationship between their expressions and the clinicopathological characteristics of patients were analyzed.Results:The positive expression rates of Beclin-1, LC3 and p62 in ESCC tissues were 32.14% (36/112), 37.50% (42/112) and 63.39% (71/112), The positive expression rates of Beclin-1, LC3 and p62 in adjacent normal esophageal mucosa tissues were 61.29% (19/31), 64.52% (20/31) and 32.26% (10/31), and the differences were statistically significant ( χ2 values ??were 8.715, 7.216 and 9.584, all P < 0.01). The positive expression rates of Beclin-1 and LC3 in ESCC were lower than those in adjacent normal esophageal mucosa tissues, and the positive expression rate of p62 in ESCC was higher than that in adjacentnormal esophageal mucosa tissues. In ESCC patients, the expression of Beclin-1 was related to histological grade, infiltration depth, TNM staging and lymph node metastasis (all P < 0.05); the expression of LC3 was related to infiltration depth and TNM staging (both P < 0.01); the expression of p62 was related to lymph node metastasis ( P < 0.01). In ESCC, the expression of LC3 was positively correlated with the expression of Beclin-1 ( r = 0.731, P = 0.001), and negatively correlated with the expression of p62 ( r = -0.215, P = 0.023). Conclusions:Autophagy plays a certain role in the occurrence and development of ESCC. Combined detection of autophagy-related genes Beclin-1, p62 and LC3 can assist clinical diagnosis and guide follow-up comprehensive treatment.

Purpose: MicroRNAs play key regulatory roles in the tumorigenesis of hepatitis B virus-related hepatocellular carcinoma (HBVHCC). This study aimed to explore the regulatory effects of microRNA-98-5p (miR-98-5p) on the proliferation, migration, invasion, and apoptosis of HBV-HCC cells, as well as the underlying mechanisms involving nuclear factor-κB-inducing kinase (NIK). Materials and Methods: The expressions of miR-98-5p and NIK in HBV-HCC tissues and cells, and the level of HBV DNA in HBVHCC cells were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion, and apoptosis of HBV-HCC cells were analyzed by cell counting kit-8, wound healing, transwell, and flow cytometry assay, respectively. The targeting relationship between miR-98-5p and NIK was predicted by StarBase3.0 and verified by dual-luciferase reporter assay. HBV-HCC xenograft tumor model was constructed in mice to observe the tumor growth in vivo. Results: The expression of miR-98-5p was declined in HBV-HCC tissues and cells. Overexpression of miR-98-5p markedly reduced the level of HBV DNA; inhibited the proliferation, migration, and invasion; and promoted the apoptosis of HBV-HCC cells. NIK was a target of miR-98-5p. Overexpression of miR-98-5p markedly decreased the protein expression of NIK in MHCC97H-HBV cells. NIK reversed the tumor-suppressing effect of miR-98-5p on HBV-HCC cells. Furthermore, overexpression of miR-98-5p significantly inhibited the xenograft tumor growth and decreased the expression of NIK in mice. Conclusion MiR-98-5p inhibits the secretion of HBV, proliferation, migration, and invasion of HBV-HCC cells by targeting NIK.

Bacteremia is a life-threating syndrome often caused by methicillin-resistant (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and -lactam antibiotic resistance in . Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on -lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of -lactam antibiotics (.., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced expression, and subsequently decreased and virulence-related regulators (.., ) and genes (.., and ) expression in the studied MRSA strain. Importantly, the synergistic effect of hypericin with -lactam antibiotic (.., oxacillin) translated into therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of -lactam resistance against MRSA through inhibition, and may allow us to repurpose the use of -lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (.., oxacillin).