Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

Aim To observe the role of salvianolic acid B(Sal B)in enhancing the survival of random skin flaps and to preliminarily explore its potential mecha-nisms.Methods The appearance,degree of edema,color and hair condition of the skin flap were evaluated seven days after operation.The vascular network and blood flow of random flaps were measured by laser Doppler flow measurement.HE staining was used to detect the growth of microvessels in random flaps.The expressions of VEGF and CD34 were detected by im-munohistochemistry,the expressions of RIPK1,2 and LC3 Ⅱ were detected by immunofluorescence,and the effects of autophagy related proteins and signaling path-ways were detected by Western blot.Results The ex-perimental results showed that Sal B induced autophagy in the random skin flaps,promoted angiogenesis,and reduced oxidative stress and necrotic apoptosis,signifi-cantly increasing the survival rate of the flaps.Immu-nohistochemistry,immunofluorescence staining,and Western blot confirmed that Sal B induced autophagy in the random skin flaps by activating TFE3 protein.Conclusion Sal B can promote autophagy in cells of random skin flaps and reduce their necrotic apoptosis by activating TFE3 protein.

Objective To explore clinical effect of allogeneic peroneal bone marrow support combined with plate internal fixation in treating Neer type Ⅳ proximal humeral fractures.Methods From December 2017 to December 2020,12 patients with Neer type Ⅳ proximal humeral fractures were treated with allogeneic peroneal bone marrow support combined with plate internal fixation,including 7 males and 5 females,aged from 56 to 78 years old;the time from injury to operation ranged from 1 to7 days.Operative time,fracture healing time and complications during follow-up were observed,and clinical efficacy was e-valuated by Constant-Murley score at the latest follow-up.Results All patients were obtained follow up for 20 to 29 months.All patients got bone healing and incisicons were healed at stage Ⅰ,operative time ranged from 95 to 138 min,blood loss ranged from 210 to 275 ml,fracture healing time ranged from 14 to 18 weeks.Two patients occurred postoperative shoulder stiffness and recovered after 2 weeks of passive exercise.There were no complications such as infection,poor wound healing,and fail-ure(fracture and loosening)of internal fixators occurred.Constant-Murley shoulder function score ranged from 69 to 89 at the latest follow up,2 patients got excellent results,9 good and 1 fair.Conclusion The application of allogeneic fibular bone mar-row placement could provide effective support for medial humerus,which is conducive to assisting reduction of fracture end,re-ducing occurrence of internal fixation failure caused by collapse of humerus head and screw perforation,and significantly im-proving function of shoulder joint.

The call of the times to"promote education informatization towards a new journey"has posed new challenges to edu-cation,and the education industry should be committed to modernizing education through education informatization.In recent years,online teaching has become the norm.In this context,our teaching team introduced short video teaching into teaching innovation to spread Animal Immunology knowledge.Animation and ideological and political elements were integrated into each video,making knowledge points from"abstract"to"concrete",which stimulated students'interest in learning and cultivate the quality of rigorous scholarship and moral cultivation.The short video comment area has become a medium for interaction between teachers and students.The real-time feedback of the data platform provides a reference for the optimization and design of teaching content.The short video teaching practice effectively solves the"pain points"in traditional teaching and makes the obscure animal immunology knowledge more understandable.Students have increased their interest in learning,using fragmented time to actively acquire knowledge,achieving the effect of improving the teaching quality of animal immunology through online teaching resources.

To investigate the expression of serine metabolism related genes and inflammatory relat-ed genes in CD4+T cells of healthy and cows with ketosis.Firstly,CD4+T cells in peripheral blood of dairy cows were isolated by magnetic bead sorting.Second,expression of serine metabolism re-lated genes PHGDH,PAST1,PSPH,SHMT1,SHMT2,SDS,SFXN1 and inflammation related genes IL-6,IFN-γ,IL-17A,FOXP3,IL-10,TGF-β in CD4+T cells in healthy and ketosis cows was detected by fluorescence quantitative PCR.The transcription levels of PHGDH,PAST1 and PSPH in CD4+T cells of ketosis cows were significantly increased compared with healthy cows(P＜0.01),the transcription level and translation level of SDS were significantly increased(P＜0.01).The transcription levels of SHMT2 were significantly decreased(P＜0.05).Transcription and translation levels of SFXN1 were significantly decreased(P＜0.05).The transcription level of SHMT1 was decreased but not significantly.Compared with healthy cows,the transcription levels of IL-6,IFN-γ and IL-17A in CD4+T cells of ketosis cows were significantly increased(P＜0.01),the transcription levels of IL-10,TGF-β and FOXP3 were significantly decreased(P＜0.05).The results showed that the expression of genes related to serine synthesis increased,the expression of genes related to serine decomposition decreased,the expression of pro-inflammatory factors increased,and the expression of anti-inflammatory factors decreased,suggesting that serine metab-olism plays an important role in the inflammatory process of dairy cows.

Objective:To observe the clinical efficacy and safety of venetoclax(VEN)combined with azacitidine(AZA)in the treatment of adult acute myeloid leukemia(AML)patients who are unfit for intensive chemotherapy.Methods:The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected,and the efficacy and safety were analyzed retrospectively.Results:After one course of treatment with VEN and AZA,16 out of 21 unfit AML patients reached complete remission(CR)/CR with incomplete hematologic recovery(CRi),2 patients reached partial remission(PR),the overall response rate(ORR)was 85.7％.Among the 16 patients with CR/CRi,13 achieved minimal residual disease(MRD)negativity.Among the 11 patients with adverse prognosis,8 achieved CR/CRi.By the deadline of follow-up,the median overall suivival(OS)of the entire cohort was not reached,with 1-year OS rate of 61.7％.The main adverse events of VEN combined with AZA were myelosuppression,gastrointestinal reactions and infections.There were 13 cases of leukopenia,7 cases of neutropenia,7 cases of anemia,4 cases of thrombocytopenia,and these hematologic adverse events were all grade 3-4.There were 11 cases with gastrointestinal reactions and 7 cases with infections.The above adverse events were controllable and tolerable.No tumor lysis syndrome or infection related death occurred.Conclusion:VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML,and it shows a good safety profile.

Objective:To investigate the effect of different isoforms of RBBP6 on the proliferation of multiple myeloma (MM) cells after alternative splicing mediated by splicing factor SRSF1. Methods:RT-PCR was used to detect the expression levels of RBBP6 mRNA splicing isoforms regulated by SRSF1. The GEO database was used to analyze the changes of RBBP6 isoform 1 in the progression of plasma cell disease,and survival analysis was used to evaluate the value of this gene in the prognosis of MM patients. In vitro loss-of-function and gain-of-function experiments were conducted by transfecting control siRNA,RBBP6 isoform 1 siRNA,empty vector (EV),OE-RBBP6 isoform 3 into MM.1S cells,then the expression levels of RBBP6 isoform 1 and RBBP6 isoform 3 were detected by real-time PCR and Western blot. CCK-8 assay was performed to detect the cell proliferation ability. Results:Knockdown of SRSF1 increased the expression of RBBP6 isoform 3 and decreased the expression of RBBP6 isoform 1. RBBP6 isoform 1 was closely related to the progression of plasma cell disease,and the high expression of RBBP6 isoform 1 was associated with poor prognosis in patients with MM. Downregulation of RBBP6 isoform 1 expression and overexpression of RBBP6 isoform 3 both reduced the proliferation ability of MM cells. And after downregulating the expression of RBBP6 isoform 1,the level of p53 protein in MM cells was significantly increased (P<0.05). Conclusion:In MM,splicing factor SRSF1 can cause alternative splicing abnormalities in RBBP6. The RBBP6 isoform 1 promotes MM cell proliferation,while the RBBP6 isoform 3 inhibits MM cell proliferation,and the mechanism may be related to regulating the p53 pathway.

Objective:To explore the relation of self-injury behavior to thyroid hormones and lipids in adoles-cent patients with depression.Methods:A total of 182 adolescent inpatients who met the diagnostic criteria for de-pression according to the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were en-rolled,including 38 cases with self-injurious behavior and 144 cases without self-injurious.The differences in vari-ous indicators between the two groups were compared,and logistic regression analysis was used to analyze factors related to self-injury in adolescents with depression.Results:The patients with self-injurious behavior had higher levels of total cholesterol and high-density lipoprotein cholesterol(HDL-C)compared to those without self-injuri-ous behavior(P＜0.05).They also had lower levels of free thyroxine compared to the group without self-injurious behavior(P＜0.05).Logistic regression analysis results showed that those with longer duration of disease(OR=1.03)and higher HDL-C levels(OR=12.75)were more likely to have self-injurious behaviors.Conclusion:Long duration of disease and high level of HDL-C may be risk factors for self-injurious behavior in adolescents with de-pression,while low level of free thyroxine may serve as a protective factor.

Objective:To explore the diagnosis and treatment strategy of complex post-sternotomy mediastinitis with exposure of artificial implants (hereinafter referred to as implants).Methods:This study was a retrospective observational study. From January 2016 to January 2023, 16 patients with complex mediastinal infection with implant exposure after thoracotomy who met the inclusion criteria were admitted to Peking University First Hospital, including 9 males and 7 females, aged from 21 to 74 years. The infected wounds were subjected to multiple thorough debridement and negative-pressure wound therapy until the infection was controlled, and contrast-enhanced magnetic resonance imaging (MRI) examination was used to guide the operation after every debridement. During the operation, 5 cases of deep mediastinal pacing lead exposure, 1 case of deep mediastinal pacing lead exposure combined with pericardial patch exposure, 5 cases of pericardial patch exposure, 3 cases of artificial blood vessel exposure, and 2 cases of artificial blood vessel exposure combined with pericardial patch exposure were observed. Partial or complete implants were removed during debridement, therefore 8 patients who completely removed the middle mediastinum implants during the operation were included in the implant complete removal group. Then, according to the defects of the sternum and its surrounding soft tissue, unilateral or bilateral pectoralis major muscle flaps were used for chest wall reconstruction. The remaining 8 patients whose implants could not be completely removed were included in the implant partial removal group. The greater omentum flaps were used to cover the implants and fill the mediastinal defects. Two weeks later, the thigh medium-thickness skin grafts were transplanted on the surface of the greater omentum flaps. After debridement, the wound area was 20 cm×6 cm to 35 cm×10 cm. The area of pectoralis major muscle flap ranged from 15 cm×8 cm to 20 cm×10 cm, and the area of greater omentum flap ranged from 30 cm×15 cm to 40 cm×25 cm. The bacterial culture and high throughput sequencing test results of wound tissue samples of all patients were counted in the first debridement surgery. The hospitalization time, the time for C reactive protein (CRP) to decrease to normal level, and the number of operations were counted for all patients, and the above indexes of the two groups of patients were compared. During the follow-up, the wound recurrence of the patients was observed.Results:The positive ratio of bacterial culture in wound tissue samples was 14/16 in the first debridement surgery, and the positive ratio of high throughput sequencing test was 16/16, with staphylococcus aureus as the bacteria causing most infection among patients. Except for one patient who died during the treatment (a patient in implant partial removal group), the hospitalization time was (56±5) d, the time for CRP to decrease to normal level was (18.9±2.2) d, and the number of operations was (4.5±0.5) times in the remaining patients. Compared with those in implant partial removal group, the length of hospital stay and the time for CRP to decline to normal level of patients in implant complete removal group were significantly shorter (with t values of 3.12 and 3.12, respectively, P<0.05), and the number of operations of patients in implant complete removal group was significantly decreased ( t=3.38, P<0.05). All 15 surviving patients were followed up for more than 6 months, and no recurrence of mediastinitis was observed. Conclusions:The treatment of complex mediastinal infection with exposed implants after thoracotomy is difficult, especially the wounds when the implants cannot be completely removed during debridement. The application of contrast-enhanced MRI examination combined with transplantation of tissue flap such as greater omentum flap and pectoralis major muscle flap can achieve good repair effect.

Objective To investigate the risk factors for bronchopulmonary dysplasia (BPD) in preterm infants,and to establish a risk prediction model. Methods A total of 120 preterm infants who were admitted to the neonatal intensive care unit of Shanghai Children's Hospital from January to December 2022 were included. According to the diagnostic criteria for BPD released by the National Institute of Child Health and Human Development in 2018,they were divided into a non-BPD group (84 infants) and a BPD group (36 infants). The clinical data of the infants and their mothers were compared between the two groups. The univariate analysis and the stepwise multivariate regression analysis were used to identify the risk factors for BPD and establish a risk prediction model. Results The results showed that a gestational age of<28 weeks,duration of noninvasive respiratory support,comorbidity with infectious pneumonia,and chorioamnionitis in the mother were independent risk factors for BPD in preterm infants (P<0.05). A nomogram model for predicting the development of BPD was established based on the risk factors,with an area under the receiver operating characteristic curve of 0.93,and the calibration curve of this nomogram had a slope of about 1. The goodness-of-fit test indicated the model fitted well (x2=8.287,P=0.406). Conclusions A gestational age of<28 weeks,duration of noninvasive respiratory support,comorbidity with infectious pneumonia,and chorioamnionitis in the mother are independent risk factors for BPD in preterm infants.