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.

Objective To identify the multi-dimensional needs of symptom management for oral cancer patients based on the journey map,and provide references for optimizing the symptom management of oral cancer patients.Methods From September 2023 to March 2024,the purposive sampling was used to select 15 perioperative oral cancer patients from a tertiary A general hospital in Zhengzhou for semi-structured interviews.The content analysis method was used to analyze the data and create a patient journey map.Results According to the time axis of diagnosis and treatment,the symptom management of patients with oral cancer was subdivided into 22 themes including identifying abnormal symptoms,clarifying diagnosis,anxiety,fear and uncertainty,guilt,high-risk behavioral inertia solidification,diagnostic trust crisis and so on from 3 dimensions of task,emotion,and pain point,and a journey map was formed.Conclusion The journey of symptom management for patients with oral cancer is long and complex,and the needs of patients'physiological and psychological symptom management are dynamically changing.In the future,the digital intelligence of big data technology can be combined to achieve whole-process,personalized and precise symptom management to improve the quality of life of oral cancer patients.

Objective:To retrospectively analyze the current status of consultation, clinical characteristics, and treatment status of patients with IgG4-related disease (IgG4-RD) in order to provide assistance and a basis for early and standardized diagnosis and treatment.Methods:IgG4-RD cases admitted to our hospital from June 2015 to October 2023 were collected. The details of patients' basic information, initial symptoms, department visits, laboratory and imaging findings, histopathological examination results, and treatment plans were recorded. A statistical descriptive analysis was performed on the data.Results:A total of 105 patients with IgG4-RD were included, with a median age of 59.0 (18.0, 78.0) years. The main departments visited were clinical immunology and gastroenterology (83.8%, 88/105). The median diagnostic duration was eight months, with a maximum of 300 months, and 33.3% (35/105) of patients needed over one year for diagnosis. 92 cases underwent histopathological examinations and IgG4 staining, with a total positivity rate of 87.0% (80/92). Among these, sixteen cases underwent pathological examination after surgery, with a positivity rate of 100%; the remaining 76 cases out of 92 underwent liver biopsy, with a positivity rate of 76.1%. Out of these, there were 22 cases from the pancreas, 21 from the submaxillary gland, nine from the labial gland, and seven each from the duodenal papilla and liver, with positivity rates of 81.8%, 81.0%, 55.6%, 85.7%, and 85.7%, respectively. Eleven cases (10.5%) with normal serum IgG4 were diagnosed based on multi-organ involvement and pathological results. 94 cases (89.5%) had elevated IgG4, with a predominance of＞2.70 g/L. The median follow-up period for the 87 cases was 14 months. Two cases had poor response, twelve patients relapsed, five cases relapsed without combined drug treatment after surgery, five cases relapsed due to drug withdrawal, and two cases relapsed while tapering off steroids.Conclusions:As a multisystem disease, IgG4-RD still faces the difficulties of time-consuming diagnosis and inappropriate treatment. Therefore, it is necessary to rely on a multidisciplinary collaboration model to improve the awareness level and promote the early and standardized diagnosis and treatment of patients with IgG4-RD.

Objective To identify the multi-dimensional needs of symptom management for oral cancer patients based on the journey map,and provide references for optimizing the symptom management of oral cancer patients.Methods From September 2023 to March 2024,the purposive sampling was used to select 15 perioperative oral cancer patients from a tertiary A general hospital in Zhengzhou for semi-structured interviews.The content analysis method was used to analyze the data and create a patient journey map.Results According to the time axis of diagnosis and treatment,the symptom management of patients with oral cancer was subdivided into 22 themes including identifying abnormal symptoms,clarifying diagnosis,anxiety,fear and uncertainty,guilt,high-risk behavioral inertia solidification,diagnostic trust crisis and so on from 3 dimensions of task,emotion,and pain point,and a journey map was formed.Conclusion The journey of symptom management for patients with oral cancer is long and complex,and the needs of patients'physiological and psychological symptom management are dynamically changing.In the future,the digital intelligence of big data technology can be combined to achieve whole-process,personalized and precise symptom management to improve the quality of life of oral cancer patients.

Objective:To retrospectively analyze the current status of consultation, clinical characteristics, and treatment status of patients with IgG4-related disease (IgG4-RD) in order to provide assistance and a basis for early and standardized diagnosis and treatment.Methods:IgG4-RD cases admitted to our hospital from June 2015 to October 2023 were collected. The details of patients' basic information, initial symptoms, department visits, laboratory and imaging findings, histopathological examination results, and treatment plans were recorded. A statistical descriptive analysis was performed on the data.Results:A total of 105 patients with IgG4-RD were included, with a median age of 59.0 (18.0, 78.0) years. The main departments visited were clinical immunology and gastroenterology (83.8%, 88/105). The median diagnostic duration was eight months, with a maximum of 300 months, and 33.3% (35/105) of patients needed over one year for diagnosis. 92 cases underwent histopathological examinations and IgG4 staining, with a total positivity rate of 87.0% (80/92). Among these, sixteen cases underwent pathological examination after surgery, with a positivity rate of 100%; the remaining 76 cases out of 92 underwent liver biopsy, with a positivity rate of 76.1%. Out of these, there were 22 cases from the pancreas, 21 from the submaxillary gland, nine from the labial gland, and seven each from the duodenal papilla and liver, with positivity rates of 81.8%, 81.0%, 55.6%, 85.7%, and 85.7%, respectively. Eleven cases (10.5%) with normal serum IgG4 were diagnosed based on multi-organ involvement and pathological results. 94 cases (89.5%) had elevated IgG4, with a predominance of＞2.70 g/L. The median follow-up period for the 87 cases was 14 months. Two cases had poor response, twelve patients relapsed, five cases relapsed without combined drug treatment after surgery, five cases relapsed due to drug withdrawal, and two cases relapsed while tapering off steroids.Conclusions:As a multisystem disease, IgG4-RD still faces the difficulties of time-consuming diagnosis and inappropriate treatment. Therefore, it is necessary to rely on a multidisciplinary collaboration model to improve the awareness level and promote the early and standardized diagnosis and treatment of patients with IgG4-RD.

Objective To investigate the impacts of wogonin(WG)on Th17/Treg cell balance in autoimmune hep-atitis(AIH)rats.Methods A total of 10 rats were randomly selected as the control group.The remaining rats were injected with concanavalin A(ConA,12.5 mg/kg)solution via tail vein to construct AIH model rat,which were ran-domly divided into AIH group,L-WG group(10 mg/kg),M-WG group(20 mg/kg),H-WG group(30 mg/kg),H-WG+VPA group(30 mg/kg WG+300 mg/kg Notch signal pathway activator VPA),10 rats in each group and administered once a day for 10 days.Serum inflammatory factors and liver function indexes were detected by ELISA;HE staining was used to observe the pathological morphology of liver tissue;the level of spleen Th17/Treg cells was detected by flow cytometry;Western blot was used to detect the expression of spleen retinoid acid related orphan receptor γ t(RORγt),fork head box protein P3(Foxp3)and liver Notch signal pathway proteins.Results The liver tissue structure of control group was normal and the staining was clear;In AIH group,the cells of liver tis-sue showed edema,the increase of cell volume led to the compression and narrowing of liver sinuses,and a large number of inflammatory cell infiltration and a small amount of necrosis occurred.The contents of alanine aminotrans-ferase(ALT),aspartate aminotransferase(AST),interleukin(IL)-17 and IL-23,level of Th17 cells,Th17/Treg,the expression of RORγt,Notch,hes family bHLH transcription factor 1 gene(HES1)and hes related family bHLH transcription factor with YRPW motif 1(HEY1)protein in AIH group were greatly higher than those in control group(P＜0.05),the contents of IL-10 and TNF-β,level of Treg cells,and level of Foxp3 protein were greatly lower(P＜0.05);Compared with AIH group,the liver injury in L-WG group,M-WG group and H-WG group was im-proved,the contents of ALT,AST,IL-17 and IL-23,level of Th17 cells,Th17/Treg,the expression of RORγt,Notch,HES1 and HEY1 protein were greatly lower(P＜0.05),the contents of IL-10 and TNF-β,level of Treg cells,and level of Foxp3 protein were greatly higher(P＜0.05);VPA reversed the improvement effect of H-WG on AIH rats.Conclusions WG could promote Th17/Treg cell balance in AIH rats by down-regulating Notch signal pathway.

Objective To investigate the effect of ursodeoxycholic acid(UDCA)on the symptoms after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in patients with primary biliary cholangitis(PBC)and their family member.Methods A questionnaire survey was conducted to collect related information from 171 PBC patients who attended The First Affiliated Hospital of Air Force Medical University before March 22,2023 and 128 family members,including demographic information,comorbidities,UDCA administration,SARS-CoV-2 infection,vaccination,symptoms,therapeutic medication,and the changes in liver disease-related symptoms.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups.Results The median age was 51 years in the PBC patients and 49 years in the family members,with no significant difference between the two groups(P>0.05).Compared with the family member group,the PBC group had significantly lower body mass index(22.2±2.4 kg/m2 vs 23.3±2.9 kg/m2,P<0.001)and proportion of male individuals(10%vs 55%,P<0.001).All PBC patients received UDCA at a dose of 13—15 mg/kg,and SARS-CoV-2 infection rate was 100%in both groups.The family members had a significantly higher SARS-CoV-2 vaccination rate than the PBC patients(91%vs 57%,P<0.001).Compared with the family members,the PBC patients had significantly milder symptoms of sneezing,nasal obstruction,chest pain,and abnormal taste(P<0.05).Compared with the family members,the PBC patients had significantly lower rates of use of compound cold medicine(11%vs 20%,P<0.05)and Lianhua Qingwen capsules(12%vs 21%,P<0.05).For the PBC patients after SARS-CoV-2 infection,the liver disease-related symptoms such as fatigue,abdominal distension,dry mouth and dry eyes,pruritus,and yellow skin were aggravated by 37%,2%,27%,10%,and 3%,respectively.Conclusion Compared with the immediate family members of PBC patients who do not take UDCA,the PBC patients receiving UDCA do not show a reduction in SARS-CoV-2 infection rate,but UDCA may have a certain effect on alleviating infection-related symptoms in such patients.PBC patients may still experience the aggravation of liver disease-related symptoms after SARS-CoV-2 infection,and the long-term effect on PBC patients after SARS-CoV-2 infection should be taken seriously in clinical practice.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.