OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics （PK）/pharmacodynamics （PD） theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration （MIC） data of colistin sulfate against Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumoniae， Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC （fAUC0－24 h/MIC） ≥15 as the target value， the probabilities of target attainment （PTA） of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC； and the expected population PTA， specifically the cumulative fraction of response （CFR）， for each regimen within a specific bacterial population was further calculated， to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL， PTA of all colistin sulfate regimens （500 000 IU， q12 h； 500 000 IU， q8 h； 750 000 IU， q12 h； 750 000 IU， q8 h； 1 000 000 IU， q12 h） were all more than 90%. When bacterial MIC＝1 µg/mL， PTA for regimen （750 000 IU， q8 h） against A. baumannii， K. pneumoniae， P. aeruginosa， E. coli and E. cloacae， and for regimen （1 000 000 IU， q12 h） against the other four bacterial species （excluding P. aeruginosa） remained above 90%. When bacterial MIC≥2 µg/mL， PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli， the CFR of only colistin sulfate regimen （500 000 IU， q12 h） was less than 90%； for K. pneumoniae， the CFR of only colistin sulfate regimen （750 000 IU， q8 h and 1 000 000 IU， q12 h） was greater than 90%； for the other three bacteria， CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL， colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL， an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.

Objective:To construct an prediction model based on magnetic resonance imaging (MRI) machine learning algorithm and radiomics and investigate its application value in predicting lymphovascular invasion (LVI) status of rectal cancer without lymph node metastasis.Methods:The retrospective cohort study was conducted. The clinicopathological data of 204 rectal cancer patients without lymph node metastasis who were admitted to Gansu Provincial Hospital from February 2016 to January 2024 were collected. There were 123 males and 81 females, aged (61±7)years. All 204 patients were randomly divided into the training dataset of 163 cases and the testing dataset of 41 cases by a ratio of 8∶2 using the electronic computer randomization method. The training dataset was used to construct the prediction model, and the testing dataset was used to validate the prediction model. The clinical prediction model, radiomics model and joint prediction model were constructed based on the selected clinical and/or imaging features. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers, and the chi-square test or Fisher exact probability were used for comparison between the groups. Comparison of ordinal data was conducted using the nonparameter rank sum test. The inter-class correlation coefficient (ICC) was used to evaluate the consistency of the radiomics features of the two doctors, and ICC >0.80 was good consistency. Univariate analysis was conducted by corres-ponding statistic methods. Multivariate analysis was conducted by Logistic stepwise regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC), Delong test, decision curve and clinical impact curve were used to evaluate the diagnostic efficiency and clinical utility of the model. Result:(1) Analysis of factors affecting LVI status of patients. Of the 204 rectal cancer patients without lymph node metastasis, there were 71 cases with positive of LVI and 133 cases with negative of LVI. Results of multivariate analysis showed that gender, platelet (PLT) count and carcinoembryonic antigen (CEA) were independent factors affecting LVI status of rectal cancer without lymph node metastasis in training dataset [ odds ratio=2.405, 25.062, 2.528, 95% confidence interval ( CI) as 1.093-5.291, 2.748-228.604, 1.181-5.410, P<0.05]. (2) Construction of clinical prediction model. The clinical prediction model was conducted based on the results of multivariate analysis including gender, PLT count and CEA. Results of ROC curve showed that the AUC, accuracy, sensitivity and specificity of clinical prediction model were 0.721 (95% CI as 0.637-0.805), 0.675, 0.632 and 0.698 for the training dataset, and 0.795 (95% CI as 0.644-0.946), 0.805, 1.000 and 0.429 for the testing dataset. Results of Delong test showed that there was no significant difference in the AUC of clinical prediction model between the training dataset and the testing dataset ( Z=-0.836, P>0.05). (3) Construction of radiomics model. A total of 851 radiomics features were extracted from 204 patients, and seven machine learning algorithms, including logistic regression, support vector machine, Gaussian process, logistic regression-lasso algorithm, linear discriminant analysis, naive Bayes and automatic encoder, were used to construct the prediction model. Eight radiomics features were finally selected from the optimal Gaussian process learning algorithm to construct a radiomics prediction model. Results of ROC curve showed that the AUC, accuracy, sensitivity and specificity of radiomics prediction model were 0.857 (95% CI as 0.800-0.914), 0.748, 0.947 and 0.642 for the training dataset, and 0.725 (95% CI as 0.571-0.878), 0.634, 1.000 and 0.444 for the testing dataset. Results of Delong test showed that there was no significant difference in the AUC of radiomics prediction model between the training dataset and the testing dataset ( Z=1.578, P>0.05). (4) Construction of joint prediction model. The joint prediction model was constructed based on the results of multivariate analysis and the radiomics features. Results of ROC curve showed that the AUC, accuracy, sensitivity and specificity of radiomics prediction model were 0.885 (95% CI as 0.832-0.938), 0.791, 0.912 and 0.726 for the training dataset, and 0.857 (95% CI as 0.731-0.984), 0.854, 0.714 and 0.926 for the testing dataset. Results of Delong test showed that there was no significant difference in the AUC of joint prediction model between the training dataset and the testing dataset ( Z=0.395, P>0.05). (5) Performance comparison of three prediction models. Results of the Hosmer-Lemeshow goodness-of-fit test showed that all of the clinical prediction model, radiomics prodiction model and joint prediction model having good fitting degree ( χ2=1.464, 12.763, 10.828, P>0.05). Results of Delong test showed that there was no signifi-cant difference in the AUC between the clinical prediction model and the joint prediction model or the radiomics model ( Z=1.146, 0.658, P>0.05), and there was a significant difference in the AUC between the joint prediction model and the radiomics model ( Z=2.001, P<0.05). Results of calibra-tion curve showed a good performance in the joint prediction model. Results of decision curve and clinical impact curve showed that the performance of joint prediction model in predicting LVI status of rectal cancer without lymph node metastasis was superior to the clinical prediction model and the radiomics model. Conclusions:The clinical prediction model is constructed based on gender, PLT count and CEA. The radiomics predictive model is constructed based on 8 selected radiomics features. The joint prediction model is constructed based on the clinical prediction model and the radiomics predictive model. All of the three models can predict the LVI status of rectal cancer with-out lymph node metastasis, and the joint prediction model has a superior predictive performance.

Objective:To study the expression of Toll like receptor 3 (TLR3) in human adenocarcinoma of the lung cells induced by respiratory syncytial virus (RSV) and its significance in the diagnosis of pneumonia in children.Methods:A549 cells were divided into RSV infection group [added 1 μg/ml Lipopolysaccharide (TLR3 agonist) transfected RSV virus after 150 μl intervention], Lipopolysaccharide stimulation group (added 1 μg/ml Lipopolysaccharide 150 μl intervention) and normal control group (normal culture). The mRNA expressions of tumor necrosis factor-α, interleukin 8, TLR3 protein and TLR3 in A549 Cells of different groups were compared. We prospectively selected 80 children with RSV infectious pneumonia admitted to Baoding Second Central Hospital from August 2019 to October 2021 as the RSV pneumonia group, and sixty children with common pneumonia were taken as the common pneumonia group, and 60 healthy children in our hospital were taken as the control group. The mRNA expression of serum TLR3 in different groups was compared, and the diagnostic efficacy of serum TLR3 in RSV pneumonia was evaluated by receiver operating characteristic.Results:There was a statistically significant difference in the expression of TLR3 protein among different groups of A549 cells ( P<0.001). The expression differences of TLR3 mRNA in different groups of A549 cells at different time points were statistically significant(all P<0.001). There was significant difference in the expression of tumor necrosis factor-α and interleukin 8 of A549 cells at different time points in different groups (all P<0.05). There was a statistically significant difference in the expression of serum TLR3 mRNA among the three groups of subjects ( F=155.237, P<0.001). The critical value for TLR3 gene diagnosis was 66.87, with corresponding sensitivity of 73.75%, specificity of 70.83%, and the area under curve (AUC) of 0.803(95% CI: 0.753-0.855). Conclusions:Respiratory syncytial virus induces human lung cancer cells and promotes disease progression through TLR3 expression; Serum TLR3 can be used for the diagnosis of RSV pneumonia.

Objective:To conduct a meta-analysis for the effects of ultra-early postoperative rehabilitation on hospital stay, complications and vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH).Methods:PubMed, Embase, Cochrane Library, WOS, CNKI, CBM and Wanfang databases were searched by computers to collect control studies on ultra-early rehabilitation of aSAH. The retrieval time limit was from the establishment of the databases to August 2021. The methodological quality of the included literature was evaluated according to Cochrane Handbook Systematic Reviews Interventions, and the Revman 5.2 software was used for meta-analysis.Results:A total of 5 articles were obtained, with a total of 413 patients. The methodological quality of the 5 studies was lower (grade C). The results of the meta-analysis showed that the average length of stay in the intervention group (mean difference –4.14, 95% confidence interval [ CI] –10.69-2.42; P=0.22] and the incidence of complications (odds ratio 0.86, 95% CI 0.40-1.83; P=0.70) were lower than those in the control group, but there was no significant difference. The incidence of cerebral vasospasm in the intervention group was lower than that in the control group, and there was significant difference (odds ratio 0.31, 95% CI 0.18-0.53; P<0.001). Conclusions:Postoperative ultra-early rehabilitation in patients with aSAH can reduce the incidence of cerebral vasospasm without increasing the incidence of complications. Therefore, the ultra-early rehabilitation can be considered. The methodological quality of the literature included in this study is lower, and high-quality randomized controlled trials are needed to further verify the effects of ultra-early rehabilitation on hospital stay, complications, and cerebral vasospasm.

Objective:To learn about the status of thyroid function and intelligence quotient (IQ) of children in areas with different iodine nutrition levels in Xinjiang Uygur Autonomous Region, and to explore the health risk of children with median urinary iodine of 200 - 299 μg/L, and to provide a basis for scientific iodine supplementation.Methods:In May 2019, in Xinjiang Uygur Autonomous Region, Altay Prefecture and Kashgar Prefecture were selected, where the median urinary iodine of children aged 8 to 10 years were 100 - 199 and 200 - 299 μg/L for three consecutive years (2017 - 2019). A stratified random sampling method was used to select 400 children aged 8 to 10 years in each of the two regions, urine and blood samples were collected to detect urinary iodine and thyroid function [thyrotropin stimulating hormone (TSH), free thyroxine (FT 4), free triiodothyronine (FT 3), anti-thyroglobulin antibody (TgAb), and anti-thyroperoxidase antibody (TPOAb)]. At the same time, children's IQ was measured and determined by Second Revision of Combined Raven's Test (CRT-C2) in China and Second Revision of Combined Raven's Test for Children-the Rural, in China (CRT-RC2). Results:The median urinary iodine of children aged 8 to 10 years in Altay Prefecture and Kashgar Prefecture was 188.6 and 250.1 μg/L, respectively. There was no statistically significant difference in thyroid function indexes TSH and FT 3 levels between the two regions ( Z = - 0.58, t = 0.49, P > 0.05), while there was statistically significant difference in FT 4 level ( t = 60.08, P < 0.001). There was no statistically significant difference in TgAb positive rate [3.6% (14/394), 4.0% (16/399)] between the two regions (χ 2 = 0.11, P = 0.736), but the difference of TPOAb positive rate [9.6% (38/394), 30.6% (122/399)] was statistically significant (χ 2 = 53.93, P < 0.001), while the difference of dual antibody positive rate [0.8% (3/394), 2.0% (8/399)] was not statistically significant ( P = 0.134). There was no statistically significant difference in the detection rates of subclinical hypothyroidism [8.9% (35/394), 11.0% (44/399)], subclinical hyperthyroidism [1.0% (4/394), 1.3% (5/399)] and hyperthyroidism [0.3% (1/394), 0.8% (3/399)] in children between the two regions ( P > 0.05). The IQ results of children in the two regions were 96.55 ± 11.36 and 89.57 ± 12.35, respectively, and there was no significant difference between them ( t = 2.79, P = 0.095). Conclusions:The thyroid function status of children is similar in the two regions with median urinary iodine of 100 - 199 μg/L and 200 - 299 μg/L in children aged 8 to 10 years, but the TPOAb positive rate is significantly different. Children whose iodine nutritional level is at or above the appropriate level have no obvious changes in intelligence. It is suggested that median urinary iodine at 200 - 299 μg/L is a relatively safe iodine nutrition state.

A comprehensive profiling of the vaginal microbial communities and their variability enables an accurate description of the microbiome in women.However,there is a lack of studies available on Chinese women.In the present study,the composition of the vaginal microbiota during pregnancy and the 6-week postpartum period of 454 Chinese women was characterized by sequenc-ing the V3-V4 region of the 16S ribosomal RNA(rRNA)gene.The vaginal microbiome showed variations during pregnancy and the postpartum period based on the abortion history,hypertensive disorders,delivery mode,and maternal age.Co-variation of 22 bacterial taxa,including the Lacto-bacillus genus and two of its species,may account for the common characteristics of the vaginal microbiome under scenarios of different medical histories and pregnancy outcomes.In contrast,dis-criminant bacterial species were significantly different between women who had preterm birth(PTB)with and without premature rupture of membranes(PROM),and the community state type(CST)Ⅳ-A without any predominant Lactobacillus species in the microbiota was more prevalent during pregnancy in the PROM-PTB cases,suggesting that specific bacterial species could be considered to distinguish between different types of PTB.By providing data on Chinese women,this study will enrich the knowledge of the human microbiome and contribute to a better understanding of the association between the vaginal microbiome and reproductive health.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Objective To evaluate the efficacy of interventional therapy via apical approach in complex mitral valve paravalvular leakage (PVL).Methods From January 2014 to December 2016,interventional therapy by apical approach was used in 7 patients with mitral valve PVL after mechanical valve replacement.There were 5 male and 2 female with mean age of 42-64 (51.3 ± 7.1) years.Six patients had a history of previous infective endocarditis.There were 3 cases of NYHA heart function =Ⅲ,and 4 cases =Ⅳ.The period of time between interventional therapy and previous operation was 6.5-8 (3.6 ± 3.1) years,with mitral regurgitation volume:9.5-23.1 (13.3 ± 4.7)ml.Interventional therapy of small incision method via the left sixth intercostal was carried out in the catheterization laboratory or the hybrid operation room with the patient under general anesthesia.Follow-up evaluation included peri-operational mortality,complications,improvement of cardiac function,hemolysis and postoperative residual mitral regurgitation.Results The success rate of total operation was 100％.The average operation time was 90-300 (145.7 ± 71.8) min,and the DSA radiation time was 6-25 (12.1 ± 6.5)min,with average hospitalization time of 5-12 (10.2 ± 3.5)d.The main post-operative complications included 1 case of hemoptysis,1 case of hematuria and acute renal failure,and 2 cases of blood transfusion,with blood transfusion volume of 1 200 ml and 3 290 ml,respectively.During the follow-up,there was no death.Mitral regurgitation volume decreased to 0 -1.0(0.43 ± 0.45) ml (P ＜ 0.05).All patients had improved heart function in different degree and no serious complications.Conclusions Interventional therapy via apical approach in complex mitral valve PVL has the advantages of being a simpler and safer approach,less trauma,shorter time of hospitalization,faster post-operative recovery and lower treatment cost.Its disadvantages are high difficult operation,strict indications and high technical requirements for the surgeon.By improving operation skills,choosing individualized occluders and treatment of early hemolytic complications,the success rate and long-term effect of interventional therapy can get further improved.

OBJECTIVEBoth of gp91(phox) (an isoform of nicotinamide adenine dinucleotide phosphate-reduced oxidases) and Src (a non-receptor protein tyrosine kinase) play a prominent role in mediating hypoxia/reoxygenation injury of neurons. The present study was designed to investigate the neuroprotective effect of equol, a predominant active metabolite of daidzein, against hypoxia/reoxygenation injury in rat pheochromocytoma cell line (PC12) and explore the underlying mechanisms.

METHODSPC12 cells exposed to hypoxia/reoxygenation injury were examined for reactive oxygen species (ROS) using dihydroethidium and 2', 7'-dichlorofluorescein diacetate and analyzed for changes in lactate dehydrogenase (LDH) activity and malondialdehyde (MDA) content. The expression levels of gp91(phox) and phosphorylated Src-Tyr416 (p-Src) were measured using Western blotting.

RESULTSEquol dose-dependently restored the cell viability and decreased LDH activity and MDA content in culture medium of PC12 cells exposed to hypoxia/reoxygenation. Pretreatment of the cells with 10(-5) and 10(-6) mol/L equol inhibited hypoxia/reoxygenation-induced increase of ROS. PC12 cells treated with equol prior to hypoxia/reoxygenation injury showed significant enhancement of the protein levels of gp91(phox) and p-Src.

CONCLUSIONEquol confers neuroprotection against hypoxia/reoxygenation injury in PC12 cells by inhibiting the generation of ROS very likely as a result of down-regulation of gp91(phox) and inhibition of Src phosphorylation.

Animals ; Cell Hypoxia ; Cell Survival ; Down-Regulation ; Equol ; pharmacology ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Membrane Glycoproteins ; metabolism ; NADPH Oxidase 2 ; NADPH Oxidases ; metabolism ; Neurons ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; PC12 Cells ; Phosphorylation ; Rats ; Reactive Oxygen Species ; metabolism ; src-Family Kinases ; metabolism

Venous thromboembolism includes deep venous thrombosis and pulmonary embolism. It is a more common and preventable complication in neurology. The prevention of venous thromboembolism is an important component in the treatment of the patients with cerebral hemorrhage. The measures include mechanical prevention and drug prevention. The mechanical prevention measures include intermittent pneumatic compression devices and pressure gradient elastic stockings. Studies have suggested that anticoagulants also plays an important role in the prevention of venous thromboembolism. The comprehensive and systematic understanding of the prevention of venous thromboembolism wil help to guide the clinical therapy and improve the outcomes of patients after primary intracerebral hemorrhage.