Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity, expanding antibacterial spectra, and reducing required dosages. Previously, compound 15 was identified as a potential adjuvant for Polymyxin B (PB) against multidrug-resistant (MDR) Pseudomonas aeruginosa DK2; however, its clinical utility was hindered by high cytotoxicity, uncertain in vivo efficacy, and an unclear synergetic mechanism. To address these challenges, we synthesized and evaluated a series of novel benzamide derivatives, with A22 emerging as a particularly promising candidate. A22 demonstrated potent synergistic activity to PB, minimal cytotoxicity, improved water solubility, and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains. In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22. Moreover, A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2. Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production, reducing ATP levels, increasing NOX activity, and inhibiting biofilm formation, leading to bacterial death. These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants, offering a robust approach to combating MDR Gram-negative bacterial infections.

Objective To investigate the clinical value of serum interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in combination with pulmonary function indicators in identifying severe Mycoplasma pneumoniae pneumonia (MPP) in children. Methods A total of 102 children with severe MPP were selected as the study subjects (severe group), and another 102 children with mild MPP treated during the same period were selected as the mild group. The serum levels of IL-6, IL-8 as well as forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₁ percentage of predicted (FEV₁%pred) and the ratio of FEV₁ to FVC at the time of admission of children in each group were compared. Results The serum levels of IL-6 and IL-8 in the severe group were significantly higher than those in the mild group, while the FVC, FEV₁%pred, and FEV₁/FVC% were significantly lower than those in the mild group (P < 0.05). The serum levels of IL-6 and IL-8 were negatively correlated with FVC, FEV₁%pred and FEV₁/FVC% (P < 0.05). The area under the curve (AUC) for assessing the severity of MPP for IL-6, IL-8, FVC, FEV₁%pred and FEV₁/FVC% was 0.894 (0.849 to 0.939), 0.842 (0.787 to 0.897), 0.896 (0.851 to 0.942), 0.787 (0.725 to 0.849) and 0.744 (0.676 to 0.812), respectively. The AUC for the combined assessment of the above five parameters was 0.985 (0.973 to 0.997). Conclusion Serum IL-6, IL-8 and pulmonary function indicators can reflect the severity of MPP in children. Their combined detection can be used to differentiate between mild and severe MPP in children early and timely.

Rats ; Animals ; Sciatic Neuropathy ; Muscle, Skeletal ; Sciatic Nerve/physiology* ; Sequence Analysis, RNA ; Nerve Regeneration/physiology*

Objective:To conduct visual analysis of relevant literature on the nursing of patients with nasopharyngeal carcinoma radiotherapy, so as to provide a reference for the nursing of patients with nasopharyngeal carcinoma radiotherapy.Methods:The relevant research in China National Knowledge Infrastructure (CNKI) and Wanfang Data was searched, and the search time limit was from the establishment of the database to June 30, 2021. The volume of publications, authors, institutions, keywords and hot words were visualized in bibliometric analysis with the CiteSpace and Prism software.Results:A total of 450 relevant articles were screened out, and the total number of publications was on the rise. Research institutions in Guangxi was in an advantageous position in research, and there was still a lack of cooperation among different institutions. Current research hotspots in nursing care of patients with nasopharyngeal carcinoma undergoing radiotherapy revolved around formulating standardized nursing service procedures, nursing care for complications after radiotherapy, and providing complete comprehensive nursing interventions.Conclusions:Nursing care of patients undergoing radiotherapy for nasopharyngeal carcinoma has received continuous attention, and more and more innovative nursing methods and advanced nursing models have been applied to clinical practice. It is necessary to strengthen the construction of team collaboration network and conduct in-depth research on the comprehensive nursing management model.

OBJECTIVE：To provide refere nce f or the quality control and evaluation of rice-wine processed Coptidis Rhizoma decoction piece. METHODS ：Taking 17 batches of rice-wine processed Coptidis Rhizoma decoction piece from different manufacturers as samples ，HPLC method was adopted to determine the contents of 4 kinds of alkaloids as epiberberine ，coptisine， palmatine and berberine. The compound weights of epiberberine ，berberine，palmatine and berberine were calculated by the subjective and objective combination weighting method （AHP combined with variation coefficient ）. Then the quality evaluation method was used to evaluate the quality of decoction pieces combined with the appearance of decoction pieces and the contents of 4 alkaloids. The percent mass constant was calculated and the grade of rice-wine processed Coptidis Rhizoma decoction piece was classified. RESULTS ：According to the results of content determination of 4 kinds of alkaloids ，among 17 batches of samples ，a total of 13 batches of samples met the requirements of 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. Mass constants of 13 batches of qualified samples were 10.03-26.96，and the percent mass constants were 37.20％-100％. If the percent mass constant ≥ 80％ of the sample was listed as the first-class product ，the sample with the percent mass constant between 50％-＜80％ was classified as the second-class product ，and the rest was listed as the third-class product ，therefore the quality constant of first-class product was ≥21.57，that of second-class product was 13.48-＜21.57，and that of third-class product was ＜13.48. According to the grading standard ，3 batches of 13 batches of qualified samples are classified as first-class products ，6 batches are classified as second-class products ，4 batches are classified as third-class products. CONCLUSIONS ：The established subjective and objective combination weighting method and quality constant method can more scientifically and reasonably classify rice-wine processed Coptidis Rhizoma decoction piece.

Objective To investigate the influence of thrombus entrance shape, suction rate and blood flow velocity on thrombus aspiration of rotary cutting and suctioned thrombectomy devices, so as to provide theoretical support for the design and optimization of such devices. Methods Three models with different thrombus entrance shapes (‘L’-style, ‘8’-style and ‘0’-style) were established to study the influence of thrombus entrance shape on the thrombectomy; different suction rates (75, 100, 125, 150 mL/min) and different blood flow velocities (0-10 cm/s, at interval of 1 cm/s) were set to discuss how the suction rate and blood flow velocity affected the thrombectomy based on ‘8’-style thrombus entrance. Results The thrombus could not be aspirated evenly in ‘L’-style model, and there was no significantly difference in aspiration between ‘8’ -style model and ‘0’-style model. But the ‘8’-style model was better than ‘0’-style model in lateral thrombus suction. The suction rate that was greater than 100 mL/min provided a limited effect on improvement of thrombectomy effect. The best suction effect was reached when blood flow velocity was less than 1 cm/s, and the effect of thrombectomy was decreasing gradually with blood flow velocity increasing. Conclusions The thrombus entrance shape, suction rate and blood flow velocity had a great impact on thrombectomy greatly. A wide and short thrombus entrance shape, an appropriate increase of suction rate and decrease of blood flow velocity would contribute significantly to the improvement of thrombectomy effect. These results can be used as guidance for the optimal design of rotary cutting and suctioned thrombectomy devices.

Objective To investigate the effects of Tuina of Three Handing-Three Points on hindlimb motor function and expression of protein NogoA and its receptor NgR in the spinal cord of rats with sciatic nerve injury. Methods A total of 64 male Sprague-Dawley rats were randomly assigned to normal group (n = 16), sham group (n = 16), model group (n = 16) and Tuina group (n = 16). The model group and Tuina group prepared the sciatic nerve injury model with brace method. Tuina group received Tuina in methods of pressing, strumming and circular rubbing on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) with Tuina manipulation emulator. The rats were assessed with oblique plate test seven days after operation and 20 days after Tuina. Then, the spinal cord tissues were extracted to detect the expression of protein of NogoA and NgR with Western blotting. Results The scores of the oblique plate test decreased in the model group and Tuina group seven days after operation compared with those in the normal group (P < 0.05), while the expression NgR increased (P < 0.05). The scores of the oblique plate test increased in Tuina group compared with those in the model group 20 days after Tuina (P < 0.05), while the expression of NgR decreased (P < 0.05), similar to the normal group (P > 0.05). Conclusion Tuina of Three Handing-Three Points can improve the hindlimb motor function in rats with sciatic nerve injury, which may be related to inhibition of the expression of NgR in the spinal cord after sciatic nerve injury.

Objective To investigate the clinical efficiency of serum cystatin C as a marker of renal function to predict serum trough concentrations of vancomycin. Methods Data on trough concentrations of vancomycin(Cmea ),serum creatinine (Scr)concentrations,cystatin C( Cys C) concentrations were collected from 81 hospitalized patients who received vancomycin therapy. Predicted vancomycin trough concentrations(Cpre )were calculated based on Scr or Cys C concentrations associating with Bayesian forecasting method through NONMEM software. Finally,the correlations and distinctions between Cpre and Cmea were comparatively analyzed. Results There were both correlation between Cpre and Cmea in relation to Scr or Cys C(r = 0. 678,P<0. 01;r=0. 727,P<0. 01). Besides,the errors of mean predictive error(ME),mean absolute error(MAE)and root-mean-square error(RMSE)for Scr was - 5. 79,6. 86,9. 86 μg · mL-1 , respectively, where as the errors for Cys C was - 0. 82,5. 42, 7. 74 μg·mL-1 ,respectively. Conclusion Cystatin C is a good marker of renal function available for predicting serum vancomycin concentrations.

Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum concentrations data from 260 patients including 177 males and 83 females were collected separately from two centers. A one-compartment model was used to describe this sparse data. No significant difference was observed between two center datasets by introducing SID covariate. The final model was as CL= (θ (base0+ θ(max) x(1 -e(-θ(Age)(Age/72) and V = θ x θ (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the most significant covariate in the final model. Typical values of clearance (CL) and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76 L, respectively. Internal model validation by Bootstrap and NPDE were performed to evaluate the robustness and prediction of the final model. The median and 95% confidence intervals for the final model parameters were based on 1000 Bootstraps. External model evaluation was conducted using an independent dataset that consisted of 34 patients to predict model performance. Pharmacodynamic assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated by clearance based on the above population model. The results indicate that the conventional dosing regimen probably being suboptimal concentrations in aged patients. The approach via population pharmacokinetic of VAN combined with the relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational dose for attaining efficacy.

This study was aimed to observe the curative effect and safety of Danzhi Jiangtang Capsule ( DJC ) combined with atorvastatin on carotid artery intima-media thickness (IMT) in diabetes patients without hyper-tension . A total of 196 diabetes patients without hypertension with incrassate carotid artery IMT were randomly divided into the control group ( 98 cases ) and the treatment group ( 98 cases ) . The conventional diabetes thera-py was given to both groups . The atorvastatin of 20 mg/night was given to the control group . And the atorvas-tatin 20 mg/night added with DJC 9 . 0 g/night were given to the treatment group . The treatment course was
12 months . Carotid artery IMT , carotid atherosclerotic plaque area , FPG , FIns , HOMA-IR , HbA1c , blood lipids , hepatorenal function and etc . were examined before and after the treatment respectively . The results showed that there was a significant positive correlation between carotid artery IMT and FIns , HOMA-IR , HbAlc , LDL-C . After 12-month treatment , the total effectiveness is 85 . 87% in the treatment group . And there was significant difference compared with the control group ( P < 0 . 05 ) . The levels of FPG , FIns , HOMA-IR , HbAlc of the treatment group had no difference compared with the control group . Compared with the control group, TC and LDL-C of the treatment group was obviously decreased (P < 0.05). And HDL-C was significantly increased ( P < 0 . 05 ) . The carotid artery IMT of the treatment group decreased from ( 0 . 11 ±0 . 01 ) cm to ( 0 . 08 ± 0 . 01 ) cm . And compared with the control group , there was statistical significance ( P <0 . 05 ) . The carotid atherosclerotic plaque area of 58 cases in the treatment group decreased from ( 0 . 37 ±0.56) cm2 to (0.21 ± 0.25) cm2. However, there was no statistical significance compared to the control group. There were 5 adverse events in the control group and 9 adverse events in the treatment group . And there was no difference between two groups. It was concluded that DJC combined with atorvastatin can regulate lipid metabolism and reduce carotid artery IMT .