Geraniol attenuates cerebral ischemia-reperfusion injury in rats by regulating oxidative stress via Nrf2/HO-1 pathway / 中国药理学通报

Aim To investigate the regulatory effect of geraniol on Nrf2/HO-1 signaling pathway after cerebral ischemia-reperfusion(I/R)in rats. Methods In this experiment,all the male SD rats were randomly divided into nine groups receiving the following treatments:sham operation(sham); sham operation+200 mg·kg-1 geraniol; I/R; I/R+50 mg·kg-1 geraniol; I/R+100 mg/kg geraniol; I/R+200 mg·kg-1 geraniol; edaravone; I/R+ brusatol(Nrf2 inhibitor); I/R+200mg·kg-1 geraniol+brusatol. All rats received intraperitoneal injection of geraniol for five consecutive days before MCAO and again after MCAO. During the construction of cerebral I/R injury models,the blood vessels were isolated without any suture in the sham operation and the sham operation +200 mg·kg-1 geraniol groups while the blood vessels with suture in other groups. The damage of neurological function was evaluated by the modified rating scale for neurological function. The TTC,HE and Tunel staining methods were used to determine the cerebral infarction volume,the damage of the ischemic cortex and the apoptosis of cortical cells,respectively. The oxidative stress-related parameters then were measured. The protein expressions of Nrf2 and HO-1 were detected by immunohistochemical staining and the target protein expressions of the injured cortex were detected by Western blot. Results Compared with the model group,it was found that the geraniol treatment significantly repaired neural injury,reduced cerebral infarction volume,cerebral cortex damage and cell apoptosis. Meanwhile,geraniol intervention could significantly increase the expression of Nrf2/HO-1 protein in the right-sided cortex and reduce oxidative stress level. Conclusion Geraniol can attenuate cerebral injury induced by ischemia-reperfusion in rats via activating Nrf2/HO-1 signaling pathway.

Clinical analysis of 11 cases multisystem inflammatory syndrome associated with SARS-CoV-2 Omicron variant infection in children / 中华儿科杂志

Objective: To explore the clinical characteristics, diagnosis, treatment, and follow-up of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 Omicron variant infection. Methods: A retrospective analysis was conducted on clinical data of 11 children with MIS-C, who were admitted to the Department of Pediatrics of Peking University First Hospital from December 2022 to January 2023. Clinical characteristics, treatment, and follow-up of MIS-C were summarized in this study. Results: The 11 cases contained 7 boys and 4 girls, with an age of 4.4 (2.0, 5.5) years on admission. All the patients had fever, with a duration of 7(5, 9) days. Other clinical manifestations included rash in 7 cases, conjunctival hyperemia in 5 cases, red lips and raspberry tongue in 3 cases, lymphadenopathy in 3 cases, and swollen fingers and toes in 2 cases. There were 8 cases of digestive symptoms, 8 cases of respiratory symptoms, and 3 cases of nervous system symptoms. Eight patients had multi-system injuries, and one of them had shock presentation. All 11 patients were infected with SARS-CoV-2 Omicron BF.7 variant. The laboratory examination results showed that all cases had elevated inflammatory indicators, abnormal coagulation function and myocardial damage. Six patients had elevated white blood cell counts, 5 cases had liver function abnormalities, 3 cases had kidney function abnormalities, and 8 cases had coronary artery involvement. All 11 patients received anti-infection treatment, of which 3 cases received only 2 g/kg intravenous immunoglobulin (IVIG), while the remaining 8 cases received a combination of IVIG and 2 mg/(kg·d) methylprednisolone. Among the 8 cases with coronary artery disease, 6 cases received low molecular weight heparin anticoagulation therapy. All patients were followed up in 2 weeks after being discharged, and their inflammatory markers had returned to normal by that time. The 8 cases with coronary artery disease and 3 cases with pneumonia showed significant improvement or back to normal at the 4-week follow-up. All patients had no new complications or comorbidities during follow-up of more than 3 months. Conclusions: MIS-C may present with Kawasaki disease-like symptoms, with or without gastrointestinal, neurological, or respiratory symptoms. Elevated inflammatory markers, abnormal coagulation function, and cardiac injury contribute to the diagnosis of MIS-C. IVIG and methylprednisolone were the primary treatments for MIS-C, and a favorable short-term prognosis was observed during a follow-up period of more than 3 months.

Acute kidney injury in hospitalized adults with chronic kidney disease: comparing cROCK, KDIGO, and combined criteria

Acute-on-chronic kidney disease (ACKD) increases the risk of progression of chronic kidney disease (CKD). This study aimed to evaluate the ability of a novel criteria of reference change value of the serum creatinine optimized criteria for acute kidney injury in CKD (cROCK) to detect ACKD patients. Methods: This was a retrospective observational study with a 3-year follow-up. All included patients with CKD stage 3 were evaluated using cROCK, Kidney Disease Improving Global Outcomes (KDIGO), and their combined criteria. The renal composite endpoints, major adverse cardiovascular events (MACEs), and all-cause mortality were recorded as clinical outcomes. Results: A total of 812 patients was enrolled. The cROCK criteria detected more ACKD events than did the KDIGO (68.0% vs. 59.5%, p < 0.001). Compared to KDIGO (−) & cROCK (−) group, ACKD patients diagnosed by cROCK had significantly higher hazard ratio [HR] for renal composite endpoints (HR, 3.591; p < 0.001), MACEs (HR, 1.748; p < 0.001), and all-cause mortality (HR, 2.985; p < 0.001). The patients in KDIGO (+) & cROCK (+) group had the lowest survival probability when considering renal composite endpoints, MACEs, and all-cause mortality (all p < 0.001). Furthermore, cROCK resulted in the largest area under the receiver operating characteristic curve (AUC) for predicting renal composite endpoints, and the combined criteria led to the largest AUC for predicting MACEs and allcause mortality. Conclusion: Compared to the KDIGO, the cROCK detected more ACKD events. Combining both cROCK and KDIGO criteria might improve the predictive ability for long-term outcomes in ACKD patients.

Stigma and Efficacy of Zhizhu Kuanzhong Capsules Versus Doxepin in the Treatment of Refractory Functional Dyspepsia: A Randomized Controlled Trial

Background/Aims@#Stigma related with antidepressants is prevalent in patients with functional dyspepsia. It affects medication compliance and efficacy.Herbal medicine acquired a deep-rooted cultural identity in relieving dyspeptic symptoms in Asians. The research was designed to compare the effectiveness of Zhizhu Kuanzhong capsules (ZZKZ) versus doxepin hydrochloride (doxepin) on alleviating stigma and medication nonadherence among patients with refractory FD (rFD). @*Methods@#Patients with rFD from February 2021 to February 2022 were randomly allocated to receive either doxepin (n = 56) or ZZKZ (n = 57) combined with omeprazole for 4 weeks. Medication possession ratio (MPR), the disease- and medication-associated stigma were analyzed. The scales were utilized to assess dyspeptic symptoms (Leeds Dyspepsia Questionnaire) and psychological conditions (Generalized Anxiety Disorder Questionnaire and Patient Health Questionnaire). @*Results@#The MPR values for ZZKZ were significantly higher than those for doxepin (P < 0.001). The stigma scores decreased in ZZKZ group while increased in doxepin group compared to baseline after treatment. The proportion of patients showing ZZKZ-associated stigma was significantly lower than doxepin-associated stigma (P < 0.001). The MPR values were negatively correlated with posttreatment stigma scores in both groups (P < 0.001). Dyspeptic symptoms and psychological condition were improved in both groups after treatment, with no significant difference on post-treatment Leeds Dyspepsia Questionnaire, Generalized Anxiety Disorder Questionnaire, or Patient Health Questionnaire scores between 2 groups. @*Conclusion@#ZZKZ is superior to doxepin in alleviating stigma and medication non-adherence, with comparable efficacy in improving dyspeptic symptoms and psychological condition of patients with rFD.

Long Noncoding RNA Cytoskeleton Regulator RNA Suppresses Apoptosis in Hepatoma Cells by Modulating the miR-125a-5p/ HS1-Associated Protein X-1 Axis to Induce Caspase-9 Inactivation

Background/Aims@#The involvement of long noncoding RNAs in the carcinogenesis of hepatocellular carcinoma (HCC) has been well documented by substantial evidence. However, whether cytoskeleton regulator RNA (CYTOR) could affect the progression of HCC remains unclear. @*Methods@#The relative expression of CYTOR, miR-125a-5p and HS1-associated protein X-1 (HAX-1) mRNA in HCC cells were determined via quantitative real-time polymerase chain reaction. The viability of treated HCC cells was measured by Cell Counting Kit-8 assay. Cell apoptosis was estimated by flow cytometry analysis, assessment of caspase-9 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, and Western blot of apoptosisrelated proteins. The interplay between CYTOR or HAX-1 and miR-125a-5p was validated by dual-luciferase reporter assay. @*Results@#CYTOR was upregulated and miR-125a-5p was downregulated in HCC cells. CYTOR silencing inhibited cell proliferation and promoted cell apoptosis in HepG2 and SMMC-7721 cells.miR-125a-5p was sponged and negatively regulated by CYTOR, and HAX-1 was directly targeted and negatively modulated by miR-125a-5p. Overexpression of miR-125a-5p enhanced the repressive effects of CYTOR knockdown on HCC cells, and knockdown of HAX-1 enhanced the inhibitory effects of miR-125a-5p mimics on HCC cells. @*Conclusions@#CYTOR silencing facilitates HCC cell apoptosis in vitro via the miR-125a-5p/HAX-1 axis.

Acute－on－chronic liver failure： Features and prognosis of a new clinical classification system based on onset manifestations / 临床肝胆病杂志

ObjectiveTo investigate the characteristics of intrahepatic and extrahepatic organ failure at the onset of acute－on－chronic liver failure（ACLF）， to explore the features of a new clinical classification system of ACLF， and to provide a basis for the diagnosis， treatment， prognostic analysis of the disease. MethodsA retrospective analysis was performed for the clinical data of the patients who were hospitalized Beijing YouAn Hospital， Capital Medical University， from January 2015 to October 2022 and were diagnosed with ACLF for the first time. According to the conditions of intrahepatic and extrahepatic organ failure at disease onset， they were classified into type Ⅰ ACLF and type Ⅱ ACLF. Type Ⅰ ACLF referred to liver failure on the basis of chronic liver diseases， and type Ⅱ ACLF referred to acute decompensation of chronic liver diseases combined with multiple organ failure. The clinical features of patients with type Ⅰ or type Ⅱ ACLF were analyzed， and the receiver operating characteristic （ROC） curve was used to assess the value of MELD， MELD－Na， and CLIF－C ACLF scoring system in predicting the 90－day prognosis of ACLF patients with type Ⅰ or type Ⅱ ACLF. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank－sum test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsA total of 582 patients with ACLF were enrolled， among whom there were 535 patients with type Ⅰ ACLF and 47 patients with type Ⅱ ACLF. Hepatitis B and alcoholic liver disease were the main causes in both groups， with no significant difference between the two groups （P>0.05）. Chronic non－cirrhotic liver disease （28.2%） and compensated liver cirrhosis （56.8%） were the main underlying liver diseases in type Ⅰ ACLF， while compensated liver cirrhosis （34.0%） and decompensated liver cirrhosis （61.7%） were the main underlying liver diseases in type Ⅱ ACLF， and there was no significant difference in underlying liver diseases between the patients with type Ⅰ ACLF and those with type Ⅱ ACLF （P<0.001）. The patients with type Ⅱ ACLF had significantly higher median MELD score， MELD－Na score， and CLIF－C ACLF score than those with type Ⅰ ACLF （all P<0.001）. The patients with type Ⅱ ACLF had significantly higher 28－ and 90－day mortality rates than those with type Ⅰ ACLF （38.3%/53.2% vs 15.5%/27.5%， P<0.001）. For the patients with type Ⅰ ACLF who did not progress to multiple organ failure， the patients with an increase in MELD score accounted for 63.7% in the death group and 10.1% in the survival group （P<0.001）， while for the patients with type Ⅰ ACLF who progressed to multiple organ failure， there was no significant difference in the change in MELD score between the survival group and the death group （P>0.05）. In the patients with type Ⅰ ACLF， MELD score， MELD－Na score， and CLIF－C ACLF score had an area under the ROC curve （AUC） of 0.735， 0.737， and 0.740， respectively， with no significant difference between any two scores （all P>0.05）. In the patients with type Ⅱ ACLF， CLIF－C ACLF score had a significantly higher AUC than MELD score （0.880 vs 0.560， P<0.01） and MELD－Na score （0.880 vs 0.513， P<0.01）. ConclusionThere are differences in underlying liver diseases， clinical features， and prognosis between type Ⅰ and type Ⅱ ACLF， and different prognosis scoring systems have different emphases， which provide a basis for the new clinical classification system of ACLF from the perspective of evidence－based medicine.

Assessment of adequacy of colonoscopic bowel preparation based on nomogram visualization / 中华消化内镜杂志

Objective:To establish a nomogram to evaluate the adequacy of bowel preparation before colonoscopy and to guide clinical decision-making.Methods:A total of 1 023 valid questionnaires from subjects who underwent diagnosis and treatment of colonoscopy at the digestive endoscopy center, Xiangya Hospital, Central South University from September 2020 to March 2021 were finally returned. The contents of the questionnaire mainly included the clinical characteristics, defecation habits, the number of defecation and the time of the last defecation after taking the medicine and the self-assessment results of bowel preparation before colonoscopy. Subjects' bowel preparation was graded with the Boston bowel preparation scale (BBPS) by a designated endoscopist in a single blinded method. Multivariate analyse was used to explore the influencing factors for bowel preparation adequacy, and a nomogram was drawn accordingly.Results:Based on BBPS scores, bowel preparation of 674 subjects were adequate and 349 were inadequate. Multivariate analyse identified the number of defecation per week ( OR=1.649,95% CI:1.233-2.204, P=0.001), the number of defecation after medication ( OR=3.963, 95% CI: 1.851-8.485, P<0.001), the time of the last defecation after medication ( OR=5.151, 95% CI: 1.152-23.037, P=0.032), and self-assessment of bowel preparation before examination ( OR=8.284, 95% CI: 2.042-33.601, P=0.003) were influencing factors for the adequacy of bowel preparation for colonoscopy. The area under the receiver operating characteristic curve of assessment of colonoscopic bowel preparation adequacy with nomogram visualization according to influencing factors was 0.913, optimal cutoff value was 0.824, the sensitivity was 0.746, and the specificity was 0.971 under the internal validation cohort. Conclusion:The nomogram based on the number of defecation per week, the number of defecation after medication, the time of the last defecation after medication, and self-assessment of bowel preparation before examination could evaluate the adequacy of bowel preparation before colonoscopy, which is worthy of application.

CBX7 Rejuvenates Late Passage Dental Pulp Stem Cells by Maintaining Stemness and Pro-angiogenic Ability

BACKGROUND@#Ever-growing tissue regeneration causes pressing need for large population of stem cells. However, extensive cell expansion eventually leads to impaired regenerative potentials. In this study, chromobox protein homolog 7 (CBX7) was overexpressed to rejuvenate late passage dental pulp stem cells (DPSCs-P9). @*METHODS@#The recruitment of copper ions (Cu2+ )-activated hypoxia-inducible factor-1a (HIF-1a) to the CBX7 gene promoter was confirmed by chromatin immunoprecipitation assay. Functions subsequent to Cu2+ -induced or recombinant overexpression of CBX7 on proliferation, multipotency, odontoblastic differentiation and angiogenesis were investigated in vitro, while murine subcutaneous transplantation model was used to further detect the effects of Cu2+ -induced CBX7 overexpression in vivo. @*RESULTS@#Our data displayed that CBX7 overexpression maintain proliferation and multipotency of DPSCs-P9 almost as strong as those of DPSCs-P3. Both gene level of odontoblast-lineage markers and calcium precipitation were nearly the same between CBX7 overexpressed DPSCs-P9 and normal DPSCs-P3. Moreover, we also found upregulated expression of vascular endothelial growth factor in DPSCs-P9 with CBX7 overexpression, which increased the number of capillary-like structures and migrating co-cultured human umbilical vein endothelial cells as well. These findings indicate CBX7 as an effective factor to rejuvenate late passage stem cells insusceptible to cell expansion. Cu2+ has been proved to achieve CBX7 overexpression in DPSCs through the initiation of HIF-1a-CBX7 cascade. Under Cu2+ stimulation since P3, DPSCs-P9 exhibited ameliorated regenerative potential both in vitro and in vivo. @*CONCLUSION@#Long-term stimulation of Cu2+ to overexpress CBX7 could be a new strategy to manufacture large population of self-renewing stem cells.

The mechanism of modified Gan Cao Fu Zi Decoction in the treatment of rheumatoid arthritis based on network pharmacology and experimental validation / 药学学报

We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg-1), medium (8 g·kg-1) and high (16 g·kg-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.

The expression and clinical significance of microRNA-574-3p in colon cancer / 中国医师杂志

Objective:To study the expression and clinical significance of microRNA-574-3p (miR-574-3p) in colon cancer.Methods:A total of 106 colon cancer patients who were admitted to the First Hospital of Qinhuangdao and Shijiazhuang Hospital of Traditional Chinese Medicine from June 2012 to June 2015 were selected as the research objects. Real-time fluorescent quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of miR-574-3p in colon cancer tissues and normal adjacent tissues. The relationship between the expression of miR-574-3p and the clinicopathological characteristics and prognosis of patients with colon cancer was analyzed. Immunohistochemical staining was used to detect the relationship between the expression of miR-574-3p and the expression of CyclinA2 or E-cadherin.Results:Compared with normal tissues adjacent to cancer, the expression level of miR-574-3p in 106 cases of colon cancer was significantly lower ( P<0.01). The decreased expression of miR-574-3p was related to tumor diameter, Dukes stage, histological grade and lymph node metastasis (all P<0.05), but not to age and tumor location (all P>0.05). The patients with low expression of miR-574-3p, high Dukes stage and histological grade, and lymph node metastasis had poor survival (all P<0.05). The 5-year overall survival rate of patients with decreased miR-574-3p expression in cancer tissue was significantly lower than that of patients without decreased miR-574-3p expression ( P=0.007 6). Compared with patients with no decreased miR-574-3p expression, patients with decreased miR-574-3p expression had higher CyclinA2 protein integrated optical density (IOD) value and lower E-cadherin protein IOD value in colon cancer tissues (all P<0.05). Conclusions:The decreased expression of miR-574-3p is related to the poor prognosis of colon cancer patients, which may affect tumor recurrence and metastasis by regulating the expression of CyclinA2 and E-cadherin proteins.

Application design of O2O teaching mode in military vocational education / 中华医学教育探索杂志

The military vocational education is facing the reform under the background of "Internet +" education. O2O teaching is a model that combines the online teaching resource platform with the offline traditional education, and it is consistent with the development trend of contemporary military vocational education. In this study, we analyze the comparative advantages of O2O teaching model in military vocational education, including the multi-dimensional teaching content, the interactive teaching method, and the autonomy of teaching design. In this model, students become the subject of learning, and the process of storing knowledge will be transformed into the application and creation of knowledge. This paper also elucidates the feasibility of O2O teaching in the military vocational education, and further discusses its design in application from the point of view of managers, teachers and learners.

Experimental Study on the Inhibitory Effect of Eugenol on Inflammatory Activation of Hepatic Stellate Cells by MSCs / 中山大学学报(医学科学版)

ObjectiveThis study aimed to investigate the effects of eugenol on inhibiting the inflammatory activation of human umbilical cord mesenchymal stem cells （HUC-MSCs） and the pro-inflammatory phenotype of hepatic stellate cells （HSCs） in liver fibrosis， and to explore their underlying mechanisms. MethodsHUC-MSCs were cultured and identified in vitro， and the toxicity of eugenol to HUC-MSCs was evaluated by MTT method. The effect of eugenol on the migration ability of HUC-MSCs was investigated by in vitro scratch test. The expression of α-SMA， COL1A1， Smad2/3 and p-Smad2/3 of LX-2 cells activated by TGF-β1 treated with EU-MSCs-CM and MSCs-CM were detected by WB assay. EU-MSCs-CM and MSCs-CM treated THP-1 macrophages stimulated with Lipopolysaccharide （LPS） were analyzed for the expression of surface markers CD11b， CD86， and CD206 by flow cytometry. Additionally， the expression of pro-inflammatory genes TNF-α， IL-1β， and IL-6 in THP-1 macrophages was detected by qPCR. ResultsThe results of MTT method showed that the viability of the cells remained above 90% after 24 h and 48 h treatment at 0， 7.5， 15 μg/mL. In vitro scratches showed that eugenol treatment enhanced HUC-MSCs migration. WB results showed that compared with MSCs-CM treatment， EU-MSCs-CM treatment significantly inhibited the expression of α-SMA， COL1A1， Smad2/3， and p-Smad2/3 of activated HSCs. Flow cytometry showed that compared with MSCs-CM treatment， EU-MSCs-CM treatment had a more significant inhibitory effect on CD86， a M1-type polarization marker in THP-1 macrophages. The results of qPCR experiment showed that compared with MSCs-CM treatment， EU-MSCs-CM treatment more significantly inhibited the expressions of TNF-α， IL-1β and IL-6 of THP-1 macrophage proinflammatory genes. ConclusionsEugenol enhances the inhibitory effect of HUC-MSCs on inflammatory activation of HSCs， possibly by regulating TGF-β1/Smads signaling pathway. It also enhances the inhibitory effect of HUC-MSCs on the pro-inflammatory phenotype of macrophages. Proinflammatory macrophages can promote inflammatory activation of HSCs.

Coagulation Factors for Diagnosis of Periprosthetic Joint Infection / 中山大学学报(医学科学版)

ObjectivePeriprosthetic joint infections （PJI） are currently the most calamitous complication after arthroplasty. Although achievements have been made in many markers for the diagnosis of PJI， the lack of a gold standard remains a great obstacle for early diagnosis. This study aimed to investigate the association between coagulation markers and the development of PJI in patients undergoing revision total joint arthroplasty （TJA）. MethodsWe conducted a retrospective cohort study with a total of 2 517 patients who underwent hip or knee arthroplasties from January 2011 to January 2022 （2 394 with primary TJA， 87 with aseptic revision and 36 with PJI）. We applied univariate analysis and multivariate logistic regression to analyze differences of coagulation factors between primary TJA and aseptic revision or PJI group. Receiver operating characteristic （ROC） curve and area under the curve （AUC） were used to measure the diagnostic value of coagulation factors in predicting PJI. ResultsCoagulation factors and their ratios including plasma fibrinogen （FBG）， prothrombin time （PT）， thrombin time （TT）， activated partial thromboplastin time （APTT）， platelet （PLT）， mean platelet volume （MPV）， platelet distribution width （PDW）， plateletcrit （PCT）， PLT / MPV， PLT / PDW and PLT / PCT were included in this study. High FGB level was strongly correlated with the risk of PJI compared to other coagulation factors. The optimal threshold value of FBG was 4.53 g/L with a sensitivity of 47.22%， a specificity of 93.07% （Primary TJA group vs. PJI group）. Similarly， the optimal threshold value of FBG was 4.44 g/L with a sensitivity of 47.22%， a specificity of 95.40% between the other two groups （Aseptic revision group vs. PJI group）. ROC curve analysis demonstrated moderate diagnostic performance of FBG （AUC value）， indicating a potential to be a diagnostic marker for PJI. ConclusionsFBG is significantly correlated with PJI and it can be used as a potential non-invasive marker for early detection. It may serve as a safe and cost-effective tool for assessing PJI in clinical work.

Role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury / 中国药理学通报

Aim To investigate the role of transient receptor potential ankyrin 1 receptor in remote preconditioning of trauma-induced cardioprotection against myocardial ischemia-reperfusion injury and related mechanism. Methods SD rats were randomly divided into five groups: Sham operation group(Sham), model group(IR), remote preconditioning of trauma group(RPCT), TRPA1 inhibitor+remote preconditioning of trauma group(TCS+RPCT)and TRPA1 inhibitor group(TCS). The model of myocardial ischemia/reperfusion in rats was established, and the hemodynamics was monitored throughout the process. After reperfusion, the rat heart was taken to measure the myocardial infarction area and myocardial apoptosis rate, the activity and protein expression of mitochondrial aldehyde dehydrogenase 2(ALDH2)and the expression of 4-hydroxynonenal(4-HNE)were detected. Results Compared with sham group, myocardial infarction area and myocardial apoptosis cell increased. Meanwhile, the activity and expression of ALDH2 decreased and the production of 4-HNE increased in IR group. However, compared with IR group, RPCT group had decreased myocardial infarction area and the rate of cardiomyocyte apoptosis, the activity and expression of ALDH2 increased, the production of 4-HNE decreased. And then, compared with RPCT group, TCS+RPCT group reduced the myocardial protective effect of remote preconditioning of trauma. Conclusions TRPA1 receptor mediates the effect of remote preconditioning of trauma alleviating myocardial ischemia/reperfusion injury in rats. Its mechanism may be related to regulating ALDH2 activity and protein expression, and affecting the content of 4-HNE.

Clinical characteristics and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia arising from malignant tumors / 中华血液学杂志

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.

Diagnosis and Treatment of Klebsiella Pneumoniae Combined with Enterobacter Cloacae in Lumbar Intervertebral Space Infection / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical diagnosis and treatment of rare primary lumbar intervertebral space infection with Klebsiella pneumoniae and Enterobacter cloacae， and provide clinical experience for the diagnosis and treatment of this rare spinal infection. MethodsAn elderly male patient with low back pain and numbness in the left lower extremity for more than 7 months， which aggravated for more than 1 week， was diagnosed with lumbar disc herniation after laboratory and imaging examinations. After admission， the symptoms became acutely aggravated， and re-examination of lumbar enhanced MRI showed local enhancement at the posterior edge of the L3/4 intervertebral space. The VAS score was 9 points， and the lumbar JOA score was 6 points. A posterior lumbar interbody fusion of L3-L5 was performed， and L3/4 intervertebral disc specimens were collected during the operation for bacterial culture. ResultsBacterial culture results showed Klebsiella pneumoniae and Enterobacter cloacae infection. The patient was treated with sensitive antibiotics for 6 weeks after the operation， and the patient was cured during the follow-up of half a year after the operation. ConclusionFor middle-aged and elderly patients with clinical manifestations of acute severe low back pain or lower extremity pain， the possibility of spinal infection should be considered when routine laboratory and imaging examinations suggest lumbar degenerative diseases.

Prediction, analysis and application of learning curve of tooth preparation for all ceramic crowns of maxillary central incisors / 北京大学学报(医学版)

OBJECTIVE@#To predict the learning curve of tooth preparation for all ceramic crowns of maxillary central incisors on phantom head simulators for graduate students participating in standardized dental resident training based on the modified Wright learning curve model, then to analyze and applicate the learning curve.@*METHODS@#Twelve graduate students participating in standardized dental resident training were selected to prepare the resin maxillary central incisors on phantom head simulators for all ceramic crowns 4 times. The results of preparation were evaluated by 3 prosthetic experts with at least 10 years' experience focusing on the reduction, contour, taper, shoulder, finish line, margin placement, adjacent tooth injury, and preparation time for tooth preparation. The learning rate of tooth preparation was calculated by scores of tooth preparation of 4 times. The learning curve of tooth preparation was predicted based on the modified Wright learning curve model. According to the criteria of standardized training skill examinations for dental residents in Beijing, 80 was taken as the qualified standard score. The minimum training times for tooth preparation to satisfy the qualified standard score (80) was calculated, to analyze the characteristics of learning curve and evaluate the effectiveness of tooth preparation.@*RESULTS@#The scores of 4 tooth preparation were 64.03±7.80, 71.40±6.13, 74.33±5.96, and 75.98±4.52, respectively. The learning rate was (106±4)%, which showed the learning curve an upward trend. There were no significant differences between the qualified standard score and the predicted scores of tooth preparation from the 5th preparation to the 13th preparation (P > 0.05). The predicted score of the 14th preparation was higher than the qualified standard score (P < 0.05).@*CONCLUSION@#The trend of the learning curve of tooth preparation for all ceramic crowns of maxillary central incisors on phantom head simulators for graduate students participating in standardized dental resident training is upward, which predicts the minimum training times higher than the qualified standard score is 14 times.

Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway / 中国中药杂志

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Comparison of Disease Burden Factors of Thyroid Cancer Between China and the World From 1990 to 2019 / 中国医学科学院学报

Objective To compare the prevalence and disease burden of thyroid cancer and their trends between China and the globe from 1990 to 2019.Methods With the global disease burden data in 2019,Joinpoint was used to predict the trends of the disease burden of thyroid cancer in China and the globe from 1990 to 2019,and logarithmic linear model was used to test the predicted trends.The R language was used for predictive analysis and graphic plotting of the disease burden from 2020 to 2035.Results From 1990 to 2019,the standardized incidence rate and the standardized mortality rate of thyroid cancer in China were lower than those in the globe.The standardized incidence rate in China and the globe showed an increasing trend(with the increases of 102.65% and 40.65%,respectively),while the standardized mortality rate showed a decreasing trend(with the decreases of 7.63% and 4.91%,respectively).Compared with those of the female population,the standardized incidence and mortality rates of the Chinese male population increased significantly from 1990 to 2019(the rates of change in the male population were 48.65% and 214.60%,respectively;and the rates of change in the female population were -39.01% and 60.44%,respectively).China's overall standardized years of life lost(YLL),years lived with disability(YLD),and disability-adjusted life years(DALY)rates during the 30-year period were lower than the global average.The Chinese and global populations showed the standardized YLL rate decreasing by 16.61% and 6.88% and the standardized DALY rate decreasing by 10.77% and 3.65%,respectively,while the rates of standardized YLD increased by 128.91% and 46.89%,respectively.The magnitude of DALY in China and the world was mainly influenced by YLL.The standardized incidence,mortality,and DALY rates of the Chinese male population were gradually approaching the global levels.From 1990 and 2019,thyroid cancer showed a higher mortality rate in the population with the age ≥ 75 years and a higher incidence rate in the population with the age <75 years.It is projected that from 2020 to 2035,the standardized incidence rates in China and the world will increase by 36.66% and 21.15%,respectively;the standardized mortality rates will decrease by 20.19% and 3.46%,respectively;and the standardized DALY rate is expected to decrease by 7.08% in China and increase by 4.35% in the world.Conclusions From 1990 to 2019,China's standardized incidence rate of thyroid cancer increased and had a higher increase than the global level,and the standardized mortality rate decreased,with a slightly higher decrease than the global level.However,the increases in the standardized incidence rate and mortality rate of this disease in China's ≥75 years male population were severe.Although China's disease burden of thyroid cancer showed a decreasing trend in line with the global trend as a whole,the disease burden in the Chinese males was higher than that in the females.Specifically,the disease burden due to premature death was predominant,and the burden in specific populations requires policy attention.

Application of different prognostic scores in liver transplantation decision-making for acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To compare the impact of different prognostic scores in patients with acute-on-chronic liver failure (ACLF) in order to provide treatment guidance for liver transplantation. Methods: The information on inpatients with ACLF admitted at Beijing You'an Hospital Affiliated to Capital Medical University and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2015 to October 2022 was collected retrospectively. ACLF patients were divided into liver transplantation and non-liver transplantation groups, and the two groups prognostic conditions were followed-up. Propensity score matching was carried out between the two groups on the basis of liver disease (non-cirrhosis, compensated cirrhosis, and decompensated cirrhosis), the model for end-stage liver disease incorporating serum sodium (MELD-Na), and ACLF classification as matching factors. The prognostic condition of the two groups after matching was compared. The difference in 1-year survival rate between the two groups was analyzed under different ACLF grades and MELD-Na scores. The independent sample t-test or rank sum test was used for inter-group comparison, and the χ (2) test was used for the comparison of count data between groups. Results: In total, 865 ACLF inpatients were collected over the study period. Of these, 291 had liver transplantation and 574 did not. The overall survival rates at 28, 90, and 360 days were 78%, 66%, and 62%, respectively. There were 270 cases of matched ACLF post-liver transplantation and 270 cases without ACLF, in accordance with a ratio of 1:1. At 28, 90, and 360 days, patients with non-liver transplantation had significantly lower survival rates (68%, 53%, and 49%) than patients with liver transplantation (87%, 87%, and 78%, respectively; P < 0.001). Patients were classified into four groups according to the ACLF classification criteria. Kaplan-Meier survival analysis showed that the survival rates of liver transplantation and non-liver transplantation patients in ACLF grade 0 were 77.2% and 69.4%, respectively, with no statistically significant difference (P = 0.168). The survival rate with an ACLF 1-3 grade was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.05). Patients with ACLF grades 1, 2, and 3 had higher 1-year survival rates compared to non-liver transplant patients by 50.6%, 43.6%, and 61.7%, respectively. Patients were divided into four groups according to the MELD-Na score. Among the patients with a MELD-Na score of < 25, the 1-year survival rates for liver transplantation and non-liver transplantation were 78.2% and 74.0%, respectively, and the difference was not statistically significant (P = 0.149). However, among patients with MELD-Na scores of 25-30, 30-35, and≥35, the survival rate was significantly higher in liver transplantation than that of non-liver transplantation, and the 1-year survival rate increased by 36.4%, 54.9%, and 62.5%, respectively (P < 0.001). Further analysis of the prognosis of patients with different ACLF grades and MELD-Na scores showed that ACLF grades 0 or 1 and MELD-Na score of < 30 had no statistically significant difference in the 1-year survival rate between liver transplantation and non-liver transplantation (P > 0.05), but in patients with MELD-Na score≥30, the 1-year survival rate of liver transplantation was higher than that of non-liver transplantation patients (P < 0.05). In the ACLF grade 0 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 77.8% and 25.0% respectively (P < 0.05); while in the ACLF grade 1 and MELD-Na score of≥30 group, the 1-year survival rates of liver transplantation and non-liver transplantation patients were 100% and 20.0%, respectively (P < 0.01). Among patients with ACLF grade 2, the 1-year survival rate with MELD-Na score of < 25 in patients with liver transplantation was 73.9% and 61.6%, respectively, and the difference was not statistically significant (P > 0.05); while in the liver transplantation patients group with MELD-Na score of ≥25, the 1-year survival rate was 79.5%, 80.8%, and 75%, respectively, which was significantly higher than that of non-liver transplantation patients (36.6%, 27.6%, 15.0%) (P < 0.001). Among patients with ACLF grade 3, regardless of the MELD-Na score, the 1-year survival rate was significantly higher in liver transplantation patients than that of non-liver transplantation patients (P < 0.01). Additionally, among patients with non-liver transplantation with an ACLF grade 0~1 and a MELD-Na score of < 30 at admission, 99.4% survived 1 year and still had an ACLF grade 0-1 at discharge, while 70% of deaths progressed to ACLF grade 2-3. Conclusion: Both the MELD-Na score and the EASL-CLIF C ACLF classification are capable of guiding liver transplantation; however, no single model possesses a consistent and precise prediction ability. Therefore, the combined application of the two models is necessary for comprehensive and dynamic evaluation, but the clinical application is relatively complex. A simplified prognostic model and a risk assessment model will be required in the future to improve patient prognosis as well as the effectiveness and efficiency of liver transplantation.