BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. ConclusionFor ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

Objective:To establish patient-derived organoid models of pleomorphic adenomas (PA) of the parotid gland and preliminarily characterize their histology, related biomarkers and functions.Methods:Fresh tumor tissue specimens were collected from surgical procedures of Oral and Maxillofacial Department. The harvested tissues were processed and cultured in a head and neck tumor organoid culture system to establish organoid models from parotid gland pleomorphic adenomas. The in vitro growth of PA organoids was recorded by light microscopy. The successfully established organoids were passaged and cryopreserved, and the cryopreserved PA organoids were revived and re-cultured to observe their viability and organoid regeneration ability. Histological characterization, as well as characterization and detection of related markers and functional proteins, were performed on the organoids, comparing them with the patient-derived tissues. Results:The constructed organoid model of pleomorphic adenoma exhibited a dense and compact three-dimensional spherical structure. Hematoxylin and eosin staining indicated morphological similarities between the organoid and its tissue of origin. Immunohistochemistry showed positive cytoplasmic staining for Calponin, cytokeratin 7, and epithelial membrane antigen in both the organoid and the source tumor tissue, suggesting consistent histopathological characteristics between the organoid and its tissue of origin. Periodic acid-Schiff staining of the organoid showed positive staining for glycogen, with positive staining located in the interior and periphery of the organoid, indicating that the organoid possessed secretory functions like the salivary gland.Conclusions:This study successfully constructed organoids of pleomorphic adenoma derived from patient samples. This model faithfully replicates the tissue morphology and biomarkers of the source tissue and exhibits biological functions associated with mucus secretion. It serves as a valuable in vitro model for studying the development and progression of salivary gland tumors.

Objective:To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application.Methods:A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively.Results:A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z=-1.99, P=0.047; Z=-3.01, P=0.003; Z=-2.10, P=0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2=0.79, P=0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z=-0.78, P=0.439). Conclusions:Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

Objective:To explore the clinical and electrophysiological characteristics of peripheral neuropathy in prediabetic patients.Methods:Subjects aged 20-65 years with high-risk factors of impaired glycemia enrolled in Beijing Tiantan Hospital, Capital Medical University from 2019 to 2022 were recruited to conduct oral glucose tolerance test, after excluding other causes of neuropathy or radiculopathy. Patients with impaired fasting glucose or impaired glucose tolerance were defined by American Diabetes Association criteria. These patients were divided into clinical polyneuropathy (PN) and clinical non-PN groups, according to the 2010 Toronto consensus criteria and the presence of PN symptoms and signs or not. Nerve conduction studies (NCS), F wave, sympathetic skin response (SSR), R-R interval variation (RRIV) and current perception thresholds (CPT) were performed and the abnormal rate was compared between different electrodiagnostic methods and between clinical subgroups.Results:Among the 73 prediabetic patients ultimately enrolled, only 20 (27.4%) can be diagnosed as clinical PN according to the Toronto consensus criteria. The abnormal rate of CPT (68.5%, 50/73) was significantly higher than those of F wave (2.7%, 2/73), lower limb NCS (0, 0/73), upper limb NCS changes of carpal tunnel syndrome (26.0%, 19/73), SSR (6.8%, 5/73) and RRIV (5.5%, 4/73; McNemar test, all P<0.001). With sinusoid-waveform current stimuli at frequencies of 2 000 Hz, 250 Hz and 5 Hz, the CPT device was used to measure cutaneous sensory thresholds of large myelinated, small myelinated and small unmyelinated sensory fibers respectively. CPT revealed a 21.9% (16/73) abnormal rate of unmyelinated C fiber in the hands of prediabetic patients, significantly higher than that of large myelinated Aβ fibers [8.2% (6/73), χ2=5.352, P=0.021]. Both abnormal rates of small myelinated Aδ [42.5% (31/73)] and unmyelinated C fibers [39.7% (29/73)] in the feet of prediabetic patients were significantly higher than that of large myelinated Aβ fibers [11.0% (8/73), χ2=18.508, 15.965, both P<0.001]. Compared with the clinical non-PN group, the abnormal rates of CPT [90.0% (18/20) vs 60.4% (32/53), χ2=5.904, P=0.015] and SSR [20.0% (4/20) vs 1.9% (1/53), P=0.016) were significantly higher in the clinical PN group. Conclusions:Peripheral neuropathies in prediabetic patients are usually asymptomatic or subclinical, and predispose to affect unmyelinated and small myelinated sensory fibers. Selective electrodiagnostic measurements of small fibers help to detect prediabetic neuropathies in the earliest stages of the disease.

Objective:To explore the application effect of home rehabilitation exercise prescription in non-surgical treatment of patients with lumbar disc herniation.Methods:Using the convenient sampling method, a total of 66 patients with non-surgical treatment of lumbar disc herniation who visited Outpatient Department of the First Affiliated Hospital of Zhengzhou University from January to August 2023 were selected as the research objects. The patients were divided into the control group and the observation group using the random number table method, with 33 cases in each group. The control group implemented routine home rehabilitation nursing measures, while the observation group formed an outpatient home rehabilitation nursing team based on this, constructed a home rehabilitation exercise prescription and implemented targeted home rehabilitation training. Pain Numberic Rating Scale (NRS), Oswestry Disability Index (ODI), Modified Japanese Orthopaedic Association (JOA) Scores and exercise compliance were compared between the two groups after 6 weeks of home rehabilitation.Results:After 6 weeks of home rehabilitation exercise, NRS score and ODI score of observation group were lower than those of the control group, and the differences were statistically significant ( P<0.05). The JOA score and compliance score of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Home rehabilitation exercise prescription can promote the rehabilitation of patients with non-surgical treatment of lumbar disc herniation, effectively relieve pain, improve the symptoms of limb dysfunction and improve the compliance of rehabilitation exercise.

Objective To investigate whether prophylactic anticoagulation therapy can reduce the risk of postoperative complications in patients with primary liver cancer(PLC)after hepatectomy,and to explore the influencing factors of postoperative complications.Methods The clinical data of 495 patients undergoing hepatectomy for PLC in The Third Affiliated Hospital of Naval Medical University(Second Military Medical University)from Feb.2019 to May 2021 were collected.The patients were divided into anticoagulation group(n=287,receiving prophylactic low-molecular-weight heparin after surgery)and conventional treatment group(n=208).The postoperative complications were compared between the 2 groups,and the influencing factors were analyzed using logistic regression model.Results The postoperative overall complication incidence of the 495 patients after hepatectomy was 30.7％(152/495),ranking as infection(9.1％,45/495),acute respiratory distress syndrome(ARDS;6.5％,32/495),bleeding(6.3％,31/495),post-hepatectomy liver failure(PHLF;6.1％,30/495),and venous thromboembolism(VTE;2.8％,14/495).The incidence rates of postoperative VTE,ARDS,and PHLF were significantly lower in the anticoagulation group than those in the conventional treatment group(1.4％[4/287]vs 4.8％[10/208],3.8％[11/287]vs 10.1％[21/208],and 3.8％[11/287]vs 9.1％[19/208];all P＜0.05),but there was no significant difference in the incidence of postoperative bleeding between the 2 groups(P＞0.05).Multivariate logistic regression analysis showed that age,portal hypertension,and tumor number were independent risk factors for postoperative VTE;portal hypertension,intraoperative blood loss,intraoperative blood transfusion,and preoperative procalcitonin(PCT)were independent risk factors for PHLF;ascites and preoperative bilirubin were independent risk factors for ARDS;and postoperative prophylactic anticoagulation was an independent protective factor for VTE and ARDS(all P＜0.05).Conclusion Prophylactic anticoagulation can reduce the risks of VTE,PHLF,and ARDS in PLC patients after hepatectomy,without increasing the risk of postoperative bleeding.Age,portal hypertension,number of tumors,intraoperative blood loss,intraoperative blood transfusion,ascites,preoperative PCT,and preoperative bilirubin are risk factors for postoperative complications of PLC patients after hepatectomy.

The occurrence of eosinophilic leukemia complicated with cardiogenic embolism and L?ffler endocarditis are relatively rare.Early accurate diagnosis and prompt treatment can improve the its prognosis.When patients have symptoms of neurological impairment accompanied by increased eosinophils,the rare etiological type of cerebral infarction should be actively screened.Further improvements are needed in the examination of bone marrow smears,detection of fusion genes associated with leukemia,screening for L?ffler endocarditis,and identification of intraventricular thrombi.In this case,the main manifestations of eosinophilic leukemia were cardiogenic embolism and L?ffler endocarditis.After active treatment,the symptoms improved,and the eosinophil count returned to normal.This study summarizes the case data of this patient and combines it with a literature review,with the hope of raising clinicians'understanding of this rare disease.

Objective:To construct a nomogram model for nasopharyngeal bleeding risk in nasopharyngeal carcinoma patients underwent radiotherapy, and to verify the application value of the model.Methods:From June 2020 to December 2021, 317 nasopharyngeal carcinoma patients underwent radiotherapy in the First Affiliated Hospital of Zhengzhou University were enrolled by the convenience sampling method, and divided into the bleeding group and the non-bleeding group according to the occurrence of nasopharyngeal hemorrhage bleeding. Univariate analysis and Logistic regression analysis were used to analyze the independent risk factors of nasopharyngeal hemorrhage patients underwent radiotherapy, and a nomogram model was constructed. Correction curve, Hosmer- Lemeshow ( H- L) goodness fit test and receiver operating characteristic (ROC) curve were used to evaluate the predictive efficiency of the model, and the area under ROC curve was calculated. Results:Multivariate Logistic regression analysis results showed that hypertension, skull base invasion, synchronous chemotherapy, anterior field+skull base irradiation, tumor rectum growth and average radiation dose≥70 Gy were the independent risk factors of nasopharyngeal hemorrhage in nasopharyngeal carcinoma patients underwent radiotherapy ( P<0.05). H- L goodness fit test results showed that there was no significant difference between the calibration curve predicted by the nomogram model and the ideal model curve (χ 2=3.469, P=0.614), and the area under ROC curve was 0.778 (95% CI: 0.705-0.947) . Conclusions:Hypertension, skull base invasion, synchronous chemotherapy, anterior field+skull base irradiation, tumor crypt growth and radiation dose≥70 Gy were the independent risk factors for nasopharyngeal hemorrhage in nasopharyngeal cancer patients underwent radiotherapy. The nomogram model constructed in this study has good differentiation and accuracy, which can provide a reference for medical staffs to develop targeted intervention strategies.

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis (CH) is a risk factor for myeloid malignancies remission and overall survival. Although some studies were conducted to investigate this phenomenon, the exact mechanism is still under debate. In this study, we observed that DNMT3A R878H bone marrow cells (human allele: DNMT3A R882H) displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory insult. DNMT3A R878H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation, especially TNFα insults. Mechanistically, we identified that RIPK1-RIPK3-MLKL-mediated necroptosis signaling was compromised in R878H cells in response to proliferation stress and TNFα insults. Briefly, we elucidated the molecular mechanism driving DNMT3A R878H-based clonal hematopoiesis, which raises clinical value for treating DNMT3A R882H-driven clonal hematopoiesis and myeloid malignancies with aging.