Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective:To observe the maximum tongue pressure and study the oropharyngeal activity during swallowing of patients with nasopharyngeal carcinoma (NPC) after radiotherapy so as to correlate the maximum tongue pressure with swallowing function.Methods:The mean maximum tongue pressure of nineteen NPC patients with dysphagia was measured at the anterior (TA), middle (TM) and posterior (TP) positions, followed by video fluoroscopy. Oral transit time (OTT), upper esophageal sphincter(UES)opening time (UOT) and UES opening range (UOR) were correlated with the mean maximum tongue pressures.Results:The maximum pressure at the TM and TP positions was significantly negatively correlated with OTT, but there was no significant correlation with the anterior readings. The maximum pressures at all three tongue positions were, however, positively correlated with UOT and UOR.Conclusion:The maximum pressure at the TA, TM and TP positions is strongly correlated with the swallowing function of NPC patients.

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ² test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Liver Neoplasms/pathology* ; Retrospective Studies ; Infusions, Intra-Arterial ; Treatment Outcome

Objective:To explore the application of reflective circulation fusion link teaching in operating room nursing teaching.Methods:A total of 60 nursing students of operating room accepted by our unit from October 2019 to October 2020 were divided into the control group (30 cases, using routine nursing instruction of operating room) and the experimental group (30 cases, taking reflective circulation fusion link teaching). The assessment results, self-directed learning ability and satisfaction with the teaching before and after the teaching were compared between the two groups. SPSS 26.0 was used for t test and chi-square test. Results:The scores of theoretical knowledge and nursing skills assessment in the two groups were improved, and the scores of the experimental group after teaching were higher than those of the control group[(92.84±5.91) vs. (87.25±7.29); (91.68±7.14) vs. (85.96±8.62)] ( P<0.05); the two groups were both improved in terms of learning awareness, learning behaviors, learning strategies, and learning evaluation and interpersonal skills dimensions, and the scores of the above-mentioned dimensions of the test group after teaching were higher than those of the control group ( P<0.05); the satisfaction scores of improving learning initiative, deepening the understanding and mastery of theoretical knowledge, and enhancing operational skills were higher than those of the control group ( P<0.05). Conclusion:The application of reflective circulation fusion link teaching in nursing students of the operating room can not only enhance the students' assessment results and self-directed learning ability, but also improve their satisfaction of the teaching.

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.
Hope ; Humans ; Lutetium ; Membranes ; Nuclear Medicine ; Prostate ; Radium ; Receptors, Peptide ; Singapore ; Theranostic Nanomedicine ; Yttrium

The concept of theranostics, where individual patient-level biological information is used to choose the optimal therapy for that individual, has become more popular in the modern era of ‘personalised’ medicine. With the growth of theranostics, nuclear medicine as a specialty is uniquely poised to grow along with the ever-increasing number of concepts combining imaging and therapy. This special report summarises the status and growth of Theranostic Nuclear Medicine in Singapore.We will cover our experience with the use of radioiodine, radioiodinated metaiodobenzylguanidine, peptide receptor radionuclide therapy, prostate specific membrane antigen radioligand therapy, radium-223 and yttrium-90 selective internal radiation therapy.We also include a section on our radiopharmacy laboratory, crucial to our implementation of theranostic principles. Radionuclide theranostics has seen tremendous growth and we hope to be able to grow alongside to continue to serve the patients in Singapore and in the region.

Background:For Chinese patients with hepatocellular carcinoma (HCC),surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor,and yet the prognosis after surgery is diverse.We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation.Methods:A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001-2008 at Zhongshan Hospital.Age,hepatitis B surface antigen,hepatitis B e antigen,partial thromboplastin time,total bilirubin,alkaline phosphatase,γ-glutamyltransferase,α-fetoprotein,tumor size,cirrhosis,vascular invasion,differentiation,encapsulation,and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion.The Harrell's concordance index (C-index) was used to measure model performance.Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient.Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009-2012,808 patients from Eastern Hepatobiliary Surgery Hospital during 2008-2010,and 244 patients from Tianjin Medical University Cancer Hospital during 2010-2011 were enrolled as external validation cohorts.Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.Results:Shanghai Score showed good calibration and discrimination in postsurgical HCC patients.The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients),and in the three independent validation cohorts,the CIs for OS ranged 0.70-0.72 and that for RFS ranged 0.63-0.68.Furthermore,Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α).The identified subset of patients at low risk could be ideal candidates for curative surgery,and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery.Finally,a web server with individualized outcome prediction and treatment recommendation was constructed.Conclusions:Based on the largest cohort up to date,we established Shanghai Score-an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery.The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.

Objective To evaluate the efficacy and safety of ER XIE TING GRANULES in children with acute diarrhea.Method A multicenter,randomized,open-label,parallel-controlled clinical trial was carried out in 15 hospitals during March 2011 to July 2012.A total of 1489 children with acute diarrhea were enrolled and divided randomly into two groups and treated with ER XIE TING GRANULES (treatment group)and smectite powder (control group).The therapeutic efficacy and adverse drug reactions were evaluated after three-day and seven-day therapy.Superiority or non-inferiority test was done for effectiveness of the treatment based on efficacy differ by more than 10％ regarded as the superiority.Result Totally 1458 children completed the study,in whom 726 children received ER XIE TING GRANULES and 732 received smectite powder.After three-day and seven-day therapy,cure rates and total efficacy rates of the treatment group were 44.2％,94.1％,88.8％,and 97.9％ separately and higher than those of control group (39.3％,88.4％,83.9％,97.4％) (Z =3.2,P ＜0.01 ;Z =2.46,P ＜0.05).There were 520 children with rotavirus infection and in whom 266 cases received ER XIE TING GRANULES and 254 received smectite powder.For rotavirus enteritis,cure rates and total efficacy rates of the treatment group after three-day and seven-day therapy were 40.6％,95.1％,89.9％,and 98.9％ separately and higher than those of control group (26.4％,84.3％,78.8％,and 96.8％) (Z=4.807,P＜0.01;Z=3.519,P＜0.01).The lower limits of the 95％ confidence interval of difference of cure rate and total efficacy rates after three-day and seven-day therapy between two groups were less than 10％.No obvious drug related adverse reactions were found during the study.Conclusion ER XIE TING GRANULES has the same effect for treatment of acute diarrhea and rotavirus enteritis in children.No obvious drug related adverse reactions were found.

OBJECTIVETo compare the morphological difference between dermal tissue of normal skin and that of scar in rat, and to explore its structural pattern.

METHODSThe full-thickness skin and the scar tissue formed 3 weeks after wound healing from SD rats were harvested as samples, which were prepared appropriately afterwards. Samples were scanned and imaged with synchrotron radiation technology, micro-CT, and phase-contrast imaging technology. The images were rebuilt with three-dimensional software.

RESULTSThe micro-CT was materialized by using X-ray generated by synchrotron radiation light source. The structure of dermal tissues was clearly shown with the assistance of phase-contrast imaging technology in the process. It was demonstrated that the dermal tissues of normal skin of rat were mainly composed of collagenous fibers, which twined together to form an olive-like structure. These olive-like structures as basic units were arranged randomly in a certain way. The collagenous fibers in dermal tissue of the scar were arranged in a parallel manner, while some fibers were crooked and arranged in a disorderly manner.

CONCLUSIONSDermal tissue of normal skin in rat has stable three-dimensional structure, and its basic structure and manner of composition are obviously different from those of scar dermal tissue.

Animals ; Cicatrix ; diagnostic imaging ; Dermis ; diagnostic imaging ; pathology ; Imaging, Three-Dimensional ; methods ; Male ; Microscopy, Phase-Contrast ; Rats ; Rats, Sprague-Dawley ; Skin ; diagnostic imaging ; Synchrotrons ; Tomography, X-Ray Computed ; Wound Healing

Objective To investigate the effects of human tissue kallikrein 1 (Ad-hKLK1) gene delivery on the neointima formation in carotid arteries of spontaneously hypertensive rats (SHRs). Methods Carotid artery restenosis was induced in male SHR rats by balloon-injury. Rats were randomly assigned into 4 groups: Sham-operated (n = 6); Angioplasty (phosphate buffered solution 50 μl, n = 8); Vector virus (control virus, 1×10~9 IU in 50 μl, n =8) and Ad-hKLK1 (Ad-hKLK1, 1×10~9 IU in 50 μl, n =8). Rats were sacrificed 4 weeks later. The wall-to-lumen area ratio and intima/media ratio in carotid artery were assessed by image analysis in HE stained sections. The mRNA bradykinin receptor(B1R and B2R) expressions were detected by RT-PCR. The protein expression of the cycle-independent kinase inhibitors p27Kip1 and p21Cip1 were determined by Western blot analysis. Results Wall-to-lumen area ratio reduced 35.6% and intima/media ratio reduced 38.8% in Ad-hKLK1 treated SHRs compared to angioplasty group (all P <0.001). The expression of p27Kip1 and p21Cip1 increased significantly in Ad-hKLK1 treated SHRs compared with angioplasty rats (all P <0.001). The mRNA expression of B2R was significantly upregulated in angioplasty rats compared with sham-operated rats (P <0.05) while mRNA expression of B1R was similar between the 2 groups. Conclusion hKLK1 gene delivery may effectively reduce neointimal formation via downregulating bradykinin B2R and up-regulating the expressions of p27Kip1, p21Cip1 signaling pathways in carotid arteries of SHRs after balloon injury.