BACKGROUND:Salvianolic acid B can inhibit cell damage induced by H2O2,effectively remove excess reactive oxygen species,and exert antioxidant properties.It has been used in the treatment of many diseases.However,there are relatively few studies on the role and mechanism of salvianolic acid B in intervertebral disc degeneration. OBJECTIVE:To observe the effect and mechanism of salvianolic acid B on oxidative stress-induced intervertebral disc degeneration by using gelatin methacryloyl hydrogel as a carrier through the in vitro cell experiment and the in vivo animal experiment. METHODS:The gelatin methacryloyl hydrogel(drug-loaded hydrogel)loaded with salvianolic acid B was prepared.(1)In vitro cell experiment:The lumbar nucleus pulposus cells of adult SD rats were isolated and extracted,and passage 3 nucleus pulposus cells were selected and divided into groups:Group A was added complete medium.In group B,a complete medium containing H2O2 was added.Group C was inoculated on methylacrylylated gelatin hydrogel and added with a complete medium containing H2O2.Group D was inoculated on methyl acrylyl gelatin hydrogel loaded with salvianolic acid B and added into a complete medium containing H2O2.The E group was inoculated on the methylacrylyl gelatin hydrogel loaded with salvianolic acid B,and the complete medium containing H2O2 and the complete medium containing TLR4 signaling pathway inhibitor were added.Cell proliferation,oxidative stress,inflammatory response,gene expression of cell matrix-associated proteins and the protein expression of TLR4/nuclear factor-kB signaling pathway were detected.(2)Animal in vivo experiment:Sixty adult SD rats were randomly divided into normal group,acupuncture group,acupuncture + salvianolic acid group,acupuncture + hydrogel group and acupuncture + loading potion gel group,with 12 rats in each group.The last four groups were treated with acupuncture to establish models of intervertebral disc degeneration and then injected with normal saline,salvianolic acid B solution,non-drug loaded gel and drug-loaded gel in turn.Imaging examination and pathological observation were performed 4 weeks after surgery. RESULTS AND CONCLUSION:(1)In vitro cell experiment:Compared with group A,the cell proliferation was decreased;the oxidative stress reaction and inflammation reaction were enhanced;the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was increased in group B(P<0.05),and the synthesis of extracellular matrix(type Ⅱ collagen,proteoglycan)was decreased(P<0.05).The protein expression of the TLR4/nuclear factor-kB signaling pathway was increased(P<0.05).Compared with group B,the cell proliferation of groups D and E was increased,the oxidative stress response and inflammatory response were weakened,and the expression of extracellular matrix degrading enzymes(matrix metalloproteinase 3,matrix metalloproteinase 13,ADAMTS4,ADAMTS5)was decreased(P<0.05),and the synthesis of extracellular matrix was increased(P<0.05).The protein expression of TLR4/nuclear factor-kB signaling pathway was decreased(P<0.05),and the effect was more significant in group E.(2)Animal in vivo experiment:4 weeks after surgery,intervertebral disc height index,index of MRI and pathological and histological grading of the intervertebral disc had improved significantly in the acupuncture+drug-loaded hydrogel group,and simply injecting hydrogel or salvianolic acid B solution can to a certain extent improve the intervertebral disc degeneration,but they are not as good as the injection of the drug-loaded hydrogel.(3)It is concluded that gelatin methacryloyl hydrogel loaded with salvianolic acid B can inhibit oxidative stress and inflammation in the degenerated intervertebral disc tissue,inhibit the degradation of extracellular matrix,and alleviate the process of intervertebral disc degeneration,which may be accomplished by inhibiting the TLR4/nuclear factor-kB signaling pathway.

【Objective】 To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. 【Methods】 A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. 【Results】 The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P<0.05). The platelet collection rate, incidence of adverse reactions to blood donation, and non-standard whole blood collection rate in large blood banks were significantly lower than those in medium and small blood banks (P<0.05). The average quality monitoring indicators for blood component preparation process of 17 blood banks were as follows: the leakage rate of blood component preparation bags was 0.03% (3/10 000), the discarding rate of lipemic blood was 3.05% (61/2 000), the discarding rate of hemolysis blood was 0.13%(13/10 000). 0.06 case had labeling errors, 8 bags had blood catheter leaks, 2.76 bags had blood puncture/connection leaks, and 0.59 cases had non-conforming consumables. The discarding rate of hemolysis blood of large blood banks was significantly lower than that of medium and small blood banks (P<0.05), and the discarding rate of lipemic blood of large and medium blood banks was significantly lower than that of small blood banks (P<0.05). The average values of quality monitoring indicators for blood supply process of 17 blood banks were as follows: the discarding rate of expired blood was 0.023% (23/100 000), the leakage rate during storage and distribution was of 0.009%(9/100 000), the discarding rate of returned blood was 0.106% (53/50 000), the service satisfaction of hospitals was 99.16% (2 479/2 500). The leakage rate of blood components during storage and distribution was statistically different with that of blood component preparation bags between different blood banks (P<0.05). There were statistically significant differences in the proportion of regular blood donors, incidence of adverse reactions, non-standard whole blood collection rate, 400 mL whole blood collection rate, double platelet collection rate, the blood bag leakage rate during preparation process, the blood components leakage rate during storage and distribution as well as the discarding rate of lipemic blood, hemolysis blood, expired blood and returned blood among large, medium and small blood banks (all P<0.05). 【Conclusion】 The establishment of a quality monitoring indicator system for blood donation services, blood component preparation and blood supply processes in Shandong has good applicability, feasibility and effectiveness. It can objectively evaluate the quality management level, facilitate the continuous improvement of the quality management system, promote the homogenization of blood management in the province and lay the foundation for future comprehensive evaluation of blood banks.

The increasing frequency of radiographic diagnostic imaging and the cumulative dose to the public from radiation has raised widespread concerns. However, accurate measurement of the radiation dose received by the human body is difficult to achieve. Monte Carlo simulation, as a numerical computational method guided by probability statistics theory, has been applied to various dose assessments, imaging optimizations, and radiation protection in radiographic diagnostic imaging. We provide a comprehensive review of the principles of the Monte Carlo method, the modelling process of Monte Carlo simulation and the progress of its application to diagnostic radiological dose estimation.

Objective:To analyze the selection of outcome indicators for randomized controlled trials (RCT) on exercise rehabilitation in patients with atrial fibrillation (AF), promote the construction of the core outcome set and provide reference for the research design of subsequent RCT.Methods:The RCT literature related to exercise rehabilitation of patients with atrial fibrillation was systematically searched from CNKI, Wanfang, VIP, PubMed, Web of Science, Embase and Cochrane Library databases, and the search period was from establishment of the databases until July 31, 2023. After literature screening, Cochrane Risk of Bias Assessment Tool was used for quality evaluation, information extraction, classification of outcome indicators, frequency of use statistics, analysis and extraction of current shortcomings in the selection of outcome indicators, and corresponding suggestions were proposed.Results:A total of 32 articles were included, and 19 RCT were evaluated twice for outcome measures. The number of outcome measures ranged from 2 to 17, with 10 RCT setting outcome measures according to primary and secondary criteria and 6 RCT setting safety outcome measures. A total of 96 outcome indicators were extracted in this study, total 266 frequency, which could be divided into 4 categories, such as safety evaluation (18 times), clinical response (75 times), patient-reported outcomes (68 times) and laboratory and other examination (105 times) .Conclusions:Existing RCT outcome indicators of exercise rehabilitation in patients with atrial fibrillation emphasize the changes in subjective feelings and objective indicators of individuals, covering four aspects such as the physical condition, exercise ability, quality of life and psychological status of individuals. However, there is a lack of uniform standards and the safety evaluation indicators are fewer. The categories of exercise rehabilitation indicators for atrial fibrillation patients extracted in this paper can provide a reference for the design of future RCT studies and promote the generation of higher quality evidence-based medical evidence.

Objective To investigate the effect of erector spinae plane block on ultrasound-based hemodynamic parameters of the arteries of the four limbs and biochemical stress indicators in patients with thoracoscopic lobectomy. Methods A total of 120 patients with thoracoscopic lobectomy were randomly divided into study group and control group, with 60 cases in each group.The study group received erector spinae plane block during surgery, while the control group received conventional anesthesia measures.Pulmonary function indicators[peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁)], ultrasound-based hemodynamic parameters of the arteries of the four limbs (maximum systolic velocity, minimum diastolic velocity, mean velocity, arterial pulsatility index, and arterial resistance index), stress indicators[cortisol (Cor), norepinephrine (NE), angiotensin Ⅱ(Ang Ⅱ), and adrenocorticotropic hormone (ACTH)], and analgesic effect were compared between the two groups at different time points[before anesthesia induction (T₀), after extubation (T₁), and after drainage tube removal (T₂)]. Results FEV₁, FVC and PEFR in both groups were significantly lower at T₁ and T₂ than at T₀, and FEV₁, FVC and PEFR in the study group were significantly higher than those in the control group at T₁ and T₂(P < 0.05).The maximum systolic velocity and arterial resistance index in both groups were significantly lower at T₁ and T₂ than at T₀, while the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly higher at T₁ and T₂ than at T₀(P < 0.05).The maximum systolic velocity and arterial resistance index in the study group were significantly higher than those in the control group at T₁ and T₂, but the minimum diastolic velocity, mean velocity and arterial pulsatility index were significantly lower than those in the control group (P < 0.05).Cor, ACTH, Ang Ⅱ and NE in both groups were significantly higher at T₂ than at T₀, and Cor, ACTH, Ang Ⅱ and NE in the study group were significantly lower than those in the control group at T₂(P < 0.05).The Prince-Henry pain score, effective compression times, and actual compression times in the study group were significantly lower than those in the control group (P < 0.05). Conclusion Application of erector spinae plane block in thoracoscopic lobectomy causes smaller fluctuations in hemodynamic parameters of the arteries of four limbs and biochemical stress indicators, with a better anesthetic effect.

ObjectiveTo improve the anti-fall capacity and safety of the smart walkers. MethodsTwo pressure sensors were placed on the handles on both sides of the walker. The confusion matrix was obtained, the corresponding operational intent labels were manually labeled, using a support vector machine (SVM) classifier for model prediction to predict the travel intent of the users. The user wore a gyroscope and the walker was equipped with a laser sensor, to measure the angular velocity, angular acceleration and the distance data, respectively, to detect the user's fall. ResultsThe classifier model established by SVM successfully predicted three operating states of the walker, namely straight ahead, left turning and right turning. The user's fall was detected by the sudden change of the following data: the combined angular velocity was greater than 100°/s, the combined angular acceleration was greater than 1.3 G, the angular acceleration of Z-axis was greater than 0.7 G or less than 0.2 G, and the distance was greater than 600 mm or less than 300 mm. ConclusionThe improvement of the walker can predict the turn intention of the user, and detect the user's fall.

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe ^-/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. The systemic antitumor therapy of advanced NSCLC has undergone renovations of chemotherapy, targeted therapy and immunotherapy, which results in greatly improved survival for patients with advanced NSCLC. Immune checkpoint inhibitors (ICIs), especially targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), has changed the treatment paradigm of NSCLC. ICIs have become the standard treatment for advanced NSCLC without epidermal growth factor receptor(EGFR) mutation or anaplastic lymphomakinase(ALK) translocation in the first- or second-line setting, and for locally advanced NSCLC following concurrent radiotherapy and chemotherapy. ICIs are also promising in adjuvant/neoadjuvant therapy. More and more ICIs have been approved domestically for the treatment of NSCLC. Led by the NSCLC expert committee of Chinese Society of Clinical Oncology (CSCO), this consensus was developed and updated based on thoroughly reviewing domestic and foreign literatures, clinical trial data, systematic reviews, experts' discussion and the consensus(2019 version). This consensus will aid domestic clinicians in the treatment of NSCLC with ICIs.
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Objective:To determine whether subpopulations may exist which are related to regulation of immunization or inflammation in bone marrow mononuclear cells (BMMNCs) from 2 elderly patients with hip fracture and whether there might be any difference in the subpopulations between them.Methods:Two elderly patients with hip fracture were enrolled in this study. Their venous blood was harvested to determine subpopulations of complement (C)3, C4, interleukins (IL)-2, IL-6, IL-10, and lymphocytes. Single cell RNA sequencing (scRNA-Seq) was used to group their BMMNCs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed of the top 20 differentially expressed genes for each subpopulation to judge the main function of each subpopulation. The subpopulations and the key genes related to regulation of immunization or inflammation were found out. The relationships were explored between subpopulations and prognosis of the patients.Results:By the venous blood indexes, IL-10 was slightly high in patient A; C3 below normal, C4 close to the lower normal limit, IL-2, IL-6 and IL-10 were significantly high, CD8 +T % was low, and CD4 +/CD8 + high in patient B. After scRNA-Seq and bioinformatics analyses, the BMMNCs in the 2 patients were divided into 5 subpopulations. GO and KEGG enrichment analyses showed that the functions of subpopulation 2 and subpopulation 4 were related to immunization or inflammation. CCL4, CCL5, LTB and CXCR4 in subpopulation 2 and C1QA, C1QB, CD14 and SPP1 in subpopulation 4 were related to the regulation of immunization or inflammation. The final prognosis of patient A was much better. The proportions of BMMNCs involved in subpopulation 2 and subpopulation 4 from patient A were higher than those from patient B [47.00% (1,431/3,045) versus 29.28% (882/3,012); 5.88% (179/3,045) versus 3.85% (116/3,012)]. Conclusions:The BMMNCs from elderly patients with hip fracture can be divided into subpopulations by scRNA-Seq. Some of the subpopulations may be related to regulation of immunization or inflammation, which may affect the post-injury immune inflammatory state and prognosis of the patients.