Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

Objective:To develop a prognostic prediction model for patients with colorectal cancer based on a peripheral blood cell composite score (PBCS) system.Methods:This retrospective observational study included patients who had primary colorectal cancer without distant metastasis, who did not undergo radiotherapy or chemotherapy before surgery, who did not receive leukocyte or platelet-raising therapy within 1 month before surgery, and whose postoperative pathology confirmed colorectal adenocarcinoma with complete tumor resection. Patients with severe anemia, infection, or hematologic diseases before surgery, as well as those with severe heart, lung, or other important organ diseases or concurrent malignant tumors, were excluded. In total, 1021 patients with colorectal cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from April 2018 to April 2020 were retrospectively included as the training set (766 patients) and the internal validation set (255 patients). Additionally, using the same criteria, 215 patients with colorectal cancer who underwent surgical treatment in another treatment group from March 2015 to December 2020 were selected as the external validation set. The "surv_cutpoint" function in R software was used to analyze the optimal cut-off values of neutrophils, lymphocytes, and platelets, and a PBCS system was established based on the optimal cut-off values. The scoring rules of the PBCS system were as follows: Neutrophils and platelets below the optimal cut-off value = 1 point, otherwise 0 points; Lymphocytes above the optimal cut-off value = 1 point, otherwise 0 points. The scores of the three cell types were added together to obtain the PBCS. Univariate and multivariate Cox regression analyses were performed to explore the correlation between patients' clinicopathological features and prognosis, and a nomogram was constructed based on the Cox regression analysis to predict patients' prognosis. The accuracy of the nomogram prediction model was validated using the C-index, calibration curve, and decision curve analysis.Results:The optimal cut-off values for neutrophils, lymphocytes, and platelets were 4.40×10 9/L, 1.41×10 9/L, and 355×10 9/L, respectively. The patients were divided into high and low groups according to the optimal cut-off values of these cells. Survival curve analysis showed that a high lymphocyte count (training set: P=0.042, internal validation: P=0.010, external validation: P=0.029), low neutrophil count (training set: P=0.035, internal validation: P=0.001, external validation: P=0.024), and low platelet count (training set: P=0.041, internal validation: P=0.030, external validation: P=0.024) were associated with prolonged overall survival (OS), with statistically significant differences in all cases. Survival analysis of different PBCS groups showed that patients with a high PBCS had longer OS than those with a low PBCS ( P<0.05). Univariate and multivariate Cox regression analysis results showed that aspirin use history, vascular thrombus, neural invasion, CA19-9, N stage, operation time, M stage, and PBCS were independent factors affecting OS (all P<0.05). The PBCS was also an independent factor affecting disease-specific survival ( P<0.05), but not progression-free survival ( P>0.05). The above independent risk or protective factors were included in R software to construct a nomogram for predicting OS. The C-index (0.873), calibration curve, and decision curve analysis (threshold probability: 0.0%–75.2%) all indicated that the nomogram prediction model had good predictive performance for OS. Conclusion:This study demonstrates that the PBCS constructed based on preoperative peripheral blood levels of neutrophils, lymphocytes, and platelets is an independent factor associated with the prognosis of patients with colorectal cancer. The nomogram model constructed based on this score system exhibits good predictive efficacy for the prognosis of these patients.

In recent years, nucleic acid therapy, as a revolutionary therapeutic tool, has shown great potential in the treatment of genetic diseases, infectious diseases and cancer. Lipid nanoparticles (LNPs) are currently the most advanced mRNA delivery carriers, and their emergence is an important reason for the rapid approval and use of COVID-19 mRNA vaccines and the development of mRNA therapy. Currently, mRNA therapeutics using LNP as a carrier have been widely used in protein replacement therapy, vaccines and gene editing. Conventional LNP is composed of four components: ionizable lipids, phospholipids, cholesterol, and polyethylene glycol (PEG) lipids, which can effectively load mRNA to improve the stability of mRNA and promote the delivery of mRNA to the cytoplasm. However, in the face of the complexity and diversity of clinical diseases, the structure, properties and functions of existing LNPs are too homogeneous, and the lack of targeted delivery capability may result in the risk of off-targeting. LNPs are flexibly designed and structurally stable vectors, and the adjustment of the types or proportions of their components can give them additional functions without affecting the ability of LNPs to deliver mRNAs. For example, by replacing and optimizing the basic components of LNP, introducing a fifth component, and modifying its surface, LNP can be made to have more precise targeting ability to reduce the side effects caused by treatment, or be given additional functions to synergistically enhance the efficacy of mRNA therapy to respond to the clinical demand for nucleic acid therapy. It is also possible to further improve the efficiency of LNP delivery of mRNA through machine learning-assisted LNP iteration. This review can provide a reference method for the rational design of engineered lipid nanoparticles delivering mRNA to treat diseases.

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 establish HPLC finger print of Leonurus japonicus granules，and to determine the contents of 4 index components such as leonurine hydrochloride ，ferulic acid ，rutin，hyperoside. METHODS The determination was performed on Inertsil TM ODS-3 column with mobile phase consisted of acetonitrile （A）-0.1％ formic acid solution （B）in the form of gradient elution；the flow rate was 1.0 mL/min，the detection wavelength was 280 nm，the column temperature was 25 ℃，and the sample size was 5 µL. Similarity Evaluation System of Chromatogram Fingerprint of TCM （2012 edition）was used for establishing the HPLC fingerprints of 10 batches of L. japonicus granules and analyzing their similarities. By comparing with HPLC fingerprints of reference substance ，the common peaks were identified. SPSS 25.0 and SIMCA 13.0 software were used for cluster analysis and principal component analysis ；the above HPLC method was used for the content determination of 4 index components in L. japonicus granules such as leonurine hydrochloride ，ferulic acid ，rutin，hyperoside. RESULTS HPLC fingerprints of 10 batches of L. japonicus granules were established ，and 16 common peaks were matched ，and 4 peaks identified were leonurine hydrochloride （peak 6），ferulic acid （peak 13），rutin（peak 14），hyperoside（peak 16）；the similarities of 10 batches of samples were all higher than 0.970. The 10 batches of samples could be divided into four categories by cluster analysis and principal component analysis；the classification results were consistent. The contents of leonurine hydrochloride ，ferulic acid ，rutin and hyperoside were 122.10-138.82 μ g/g，9.33-10.45 μ g/g，14.12-18.95 μ g/g，5.87-8.06 μ g/g，respectively. CONCLUSIONS Established HPLC fingerprint of L. japonicus granules and the method for the content determination of 4 index components are simple and easy to operate，and have high precision and good repeatability ，which provide reference for the quality evaluation of L. japonicus granules.

Objective:To analyze the effects of a novel type of polydopamine (PDA)-coated porous titanium alloy scaffolds loaded with zoledronic acid-gelatin nanoparticles (ZOL-GNPs) for topical sustained drug release on osteoclasts in vitro. Methods:After porous titanium alloy scaffolds were fabricated using electron beam melting technique and ZOL-GNPs with different ZOL concentrations (0, 1, 10, 50, 100, 500 μmol/L) were prepared by desolvation method, PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs were constructed by combining the two. The characteristics of the scaffolds were analyzed. The biomechanics of 3 different scaffolds (bare porous titanium alloy scaffolds, PDA-coated porous titanium alloy scaffolds, and PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs) were investigated. Drug release detection was carried out by high performance liquid chromatography on the 1st, 4th, 7th, 14th, 21st, and 28th days respectively. The osteoclasts were inoculated into the novel scaffolds with different ZOL concentrations. The expression of osteoclast-related genes was detected by real-time quantitative (RT)-polymerase chain reaction (PCR); the expression of osteoclast-related proteins was detected by Western-blot.Results:The PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs were successfully constructed. Electron microscope scanning showed that the GNPs were well spheroidized, smooth in surface, and uniformly dispersed, with a particle size of (243.6±63.4) nm. The ZOL-GNPs were uniformly compounded on the surface and in the pores of the scaffolds, and the spheres were regular in shape with no adhesion. The biomechanical experiments showed that the elastic moduli of the porous titanium alloy scaffolds under 3 different conditions were (1.81±0.12) GPa, (1.80±0.23) GPa and (1.81±0.15) GPa, showing no significant difference ( P> 0.05). The drug release percentage in the porous titanium alloy scaffolds was obviously high on the first day, and increased gradually and slowly in the subsequent 27 days. In the scaffolds with a low concentration ZOL, more osteoclasts adhered and proliferated; in the 50 μmol/L scaffolds, spheroid cells appeared; the spheroid cells increased and even apoptosis occurred with an increase in the ZOL concentration. RT-PCR showed that the expression of Ctsk gene and TRAP gene increased with the increased ZOL concentration, peaked in the 50 μmol/L scaffolds, and then decreased with the increased concentration, showing statistically significant differences ( P < 0.05). Western-blot showed that the expression pattern of Ctsk and TRAP was similar to that of their related genes. Conclusions:The novel PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs demonstrate good mechanical properties and an anti-osteoporosis effect via their topical sustained drug release. The scaffolds with a ZOL concentration of 50 μmol/L may exert the best effect on inhibition of osteoclasts.

Objective:To establish the norm of clinical nursing teachers' competency in tertiary first-class hospitals in northwest China.Methods:From August 2019 to February 2020, 1 077 clinical nursing teachers were selected from 12 tertiary first-class hospitals in northwest China by stratified, random and proportional sampling, and were investigated with the Clinical Nursing Teacher Competency Evaluation Scale. Descriptive statistics were carried out on the sample data, and univariate variance analysis and pairwise comparison were carried out on the multi-classification variables of age, nursing age, professional title, teaching years and the number of teachers per year. The verified data were exported to SPSS 26.0 for statistical analysis, variance analysis was used for multi-group comparison, and LSD test was used for pairwise comparison between groups.Results:①The corresponding mean norm was established by grouping the total score and the first-class index; the percentile norm was made with 5% spacing; P10, P30, P70 and P90 were selected as the grading demarcation points, and the demarcation norm was constructed. ②Factor analysis showed that there were statistical differences in personality characteristics among different ages, nursing ages and professional titles ( P<0.05), and also in professional attitudes among different nursing ages and professional titles ( P<0.05). Conclusion:The establishment of norm provides references for individuals or units to evaluate teachers' competence.

OBJECTIVE: To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. METHODS: Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP RESULTS: Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP CONCLUSIONS Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP

Objective:To establish a clustered management plan for pulmonary care of massive burn casualties (hereinafter referred to as the clustered management plan for pulmonary care), and to explore its application effects.Methods:(1) A clustered care intervention group was established, including the medical and nursing staff from the Department of Burns and Plastic Surgery, Department of Respiratory Medicine, and Department of Infection Control at the Fourth Medical Center of PLA General Hospital (hereinafter referred to as our hospital). Four major links, including pulmonary care assessment, chest and lung physical therapy, artificial airway management, and specialized infection control were sorted out according to the key points and difficulties in pulmonary care for massive burn casualties. Evidence-based nursing methods were employed to retrieve articles related to the above-mentioned four links from PubMed, Chinese Journal Full- Text Database, VIP Database and Wanfang Data using terms of " mass burn, respiratory management and airway management" and terms of "成批烧伤,肺部护理,集束化管理" , and the clustered management plan for pulmonary care was established based on reading and discussion in combination with clinical practice and experience. (2) In this non-randomized controlled study, the clustered management plan for pulmonary care was applied to 73 massive burn patients (48 males and 25 females, aged 32 (25, 38) years) who were admitted to our hospital from January 2016 to December 2019 and met the inclusion criteria, and they were included into the clustered care group; 43 massive burn patients (25 males and 18 females, aged 35 (17, 45) years) who were admitted to our hospital from January 2013 to December 2015, received routine care and met the inclusion criteria were retrospectively included into routine care group. The pulmonary infection rate and mortality of patients in the two groups were recorded during the hospital stay. Data were statistically analyzed with chi-square test, Mann-Whitney U test, and independent sample t test. Results:(1) The clustered management plan for pulmonary care included a total of 12 specific measures covering four aspects of pulmonary care. The contents in pulmonary care assessment clearly stated to include the previous medical history, history of injury, respiratory status, hoarseness, pulmonary auscultation, etc. Chest and lung physical therapy included how to guide patients to effectively cough and do pursed lip breathing and abdominal breathing exercise, etc. Artificial airway management specified the preparation for the establishment of artificial airway at clinical reception, the observation index and frequency after tracheotomy, the method of humidification, the method and frequency of sputum suction, and the management of mechanical ventilation, etc. Specialized infection control required to strengthen hand hygiene and ventilator management. (2) The pulmonary infection rate and mortality of patients in the clustered care group were 2.74% (2/73) and 4.11% (3/73), respectively, significantly lower than 25.58% (11/43) and 18.60% (8/43) in routine care group ( χ2=11.986, 5.043, P<0.05 or P<0.01). Conclusions:The clustered management plan for pulmonary care developed for massive burn casualties focuses on the major links and key points. The measures are systemic and comprehensive, simple but precise, and highly operable, covering the entire process of massive burn care, hereby reducing the pulmonary infection rate significantly and improving the success rate of treatment.

Objective:To explore the application effect of timed, step-by-step and segmented sputum suction in airway management of patients with inhalation injury.Methods:From January 2017 to December 2019, 104 patients with inhalation injury admitted to the Department of Burns and Plastic Surgery, the Fourth Medical Center of the PLA General Hospital were selected as research objects. A non-randomized controlled study was adopted, and the patients were divided into control group ( n=49) and experimental group ( n=55) according to the single and even day of admission. The control group received the routine sputum suction, and the experimental group received the method of timed, step-by-step and segmented sputum suction. We compared the general information, incidence of lung infection and the number of daily sputum suction of patients between the two groups. Results:There was no statistically significant difference in the general information of patients between the two groups ( P>0.05) . The incidence of lung infection in the experimental group was 29.09% (16/55) , which was lower than 51.02% (25/49) in the control group with a statistically significant difference ( P<0.05) . In the experimental group, the number of daily sputum suction for patients with tracheotomy was 6 (3, 6) times, the number of daily sputum suctions for patients without tracheotomy was 1 (1, 2) times, and the number of daily sputum suctions for patients with severe inhalation injury was (6.56±2.96) times, which were less than 14 (11, 19) , 3 (3, 7) , (15.40±3.75) times respectively in the control group, and the differences were statistically significant ( P<0.01) . Conclusions:The timed, step-by-step and segmented sputum suction can reduce the number of sputum suctions for patients with inhalation injury and the workload of nursing, and effectively decrease the rate of lung infection, which is worthy of clinical promotion.