BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

Objective To study the expression of N6-methyladenosine(m6A)methyltransferase-like protein 16(METTL16),Ankyrin repeat and SOCS box containing protein 4(ASB13)in elderly breast cancer tissues and their relationship with clinicopathological features and prognosis.Methods 124 elderly patients with breast cancer diagnosed and treated in the Zibo 148 Hospital from January 2019 to January 2021 were selected.Immunohistochemistry(IHC)was used to detect the expression of METTL16 and ASB13 proteins in tissues.Real time fluorescence quantitative PCR(RT-qPCR)was used to detect the expression of METTL16 mRNA and ASB13 mRNA in tissues.Pearson correlation was used for correlation analysis.Survival analysis used Kaplan-Meier curves and Log Rank tests to compare the prognostic differences among patients with different METTL16 and ASB13 expression levels.COX regression analysis was used to analyze the prognostic factors of elderly patients with breast cancer.Results The positive rate of METTL16 in cancer tissue(70.97%)was higher than that in adjacent tissues(8.06%),while the positive rate of ASB13(22.58%)was lower than that in adjacent tissues(72.58%),the differences were statistically significant(χ2=102.642,62.146,all P<0.001).METTL16 mRNA,Snail mRNA and N-cadherin(N-cd)mRNA were higher in cancer tissues than in adjacent tissues,while ASB13 mRNA was lower in adjacent tissues,the differences were statistically significant(t=40.498～48.624,all P<0.001).METTL16 mRNA was positively correlated with Snail mRNA and N-cd mRNA in cancer tissue(r=0.712,0.669,all P<0.001),while ASB13 mRNA was negatively correlated with Snail mRNA and N-cd mRNA(r=-0.734,-0.759,all P<0.001).Compared with TNM stage Ⅰ-Ⅱ and patients with high to medium differentiation,patients with TNM stage Ⅲ and low differentiation had higher positive rate of METTL16 in cancer tissue and lower positive rate of ASB13,the differences were statistically significant(χ2=5.340～10.370,all P<0.05).The 3-year progression free survival rate(73.86%)of the METTL16 positive group was lower than that of the METTL16 negative group(88.89%),the 3-year progression free survival rate(92.86%)of the ASB13 positive group was higher than that of the ASB13 negative group(73.96%),and the differences were statistically significant(Log Rank χ2=4.483,4.882,all P<0.005).METTL16 positive,TNM stage Ⅲ,poor differentiation were risk factors affecting the prognosis of elderly breast cancer,and ASB13 positive was protective factors(Wald χ2=5.056～9.267,all P<0.001).Conclusion METTL16 expression is up-regulated and ASB13 expression is down-regulated in elderly breast cancer,both of which are related to the expression of invasion and metastasis genes,and are new prognostic markers for elderly breast cancer.

Objective:To investigate the feasibility and clinical outcome of estimating the target length of the free margin of the leaflet by diameter of the prosthesis graft used to reconstruct the aortic root during the modified root remodeling procedure.Methods:This is a retrospective case series study. The clinical data of 11 patients with aortic root aneurysm who underwent modified aortic root remodeling procedure with external sub-valvular ring from July 2021 to May 2024 at Department of Cardiovascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College were analyzed. The age of the patients was (42.3±14.4) years (range:23 to 61 years), including 9 males and 2 females. The aortic valve of all patients was tri-leaflet configuration. Marfan syndrome was diagnosed in 3 cases. The diameter of the prosthesis graft was determined according to the Lansac group′s criteria based on the diameter of the aortic annulus, and a graft ring of the same diameter was used as the external sub-valvular ring. The free margin of the leaflet was treated with central plication according to the standard of “target length of free margin of the leaflet=the diameter of the selected graft+3 to 5 mm”. The surgical results and postoperative aortic valve closure function were observed.Results:All 11 patients successfully completed the operation without in-hospital death or complications. The graft with a diameter of 28 mm were used in 7 cases, 26 mm in 3 cases, and 30 mm in 1 case. 4 patients required central plication of the free margin of 3 leaflets, 2 patients required treatment of 2 leaflets, 3 patients required treatment of 1 leaflet, and 2 patients did not need treatment of the free margin of the leaflets. The functional status of aortic valve closure was significantly improved in all patients after surgery, and the degree of residual aortic regurgitation was not more than mild. After reconstruction of the aortic root, the measured effective height was (8.8±1.3) mm (range:7 to 11 mm) and the measured coaptation length was (5.2±0.9) mm (range:4 to 7 mm). All patients were re-examined 3 months after surgery. Echocardiography showed that the degree of aortic regurgitation was mild or lower, and the left ventricular end-diastolic diameter was (49.4±6.1) mm (range: 36 to 56 mm), which was smaller than that before the operation ((58.5±7.0) mm (range: 47 to 72 mm)). Eight patients were followed up for more than 6 months, and 5 patients were followed up for more than 1 year. The degree of aortic regurgitation in these patients was mild or below.Conclusions:The method based on the diameter of the selected prosthesis graft to deal with the length of the free margin of the leaflet can be effectively used in the modified aortic root remodeling procedure with external sub-valvular ring. The early postoperative results are satisfactory .

Tumor microenvironment plays a key role in oncogenesis, development and therapeutic response. In recent years, scholars at home and abroad have paid more and more attention to the regulation of tumor microenvironment. Radiation therapy, as an important means of tumor treatment, not only kills tumor cells directly, but also affects the efficacy of radiation therapy by influencing natural killer (NK) cells to regulate the tumor microenvironment. In this article, the research progress in the regulation of tumor microenvironment by radiation therapy through NK cells was reviewed, including the mechanism of NK cell regulation by radiation therapy, the functional changes of NK cells in the tumor microenvironment, as well as the therapeutic strategies based on the above mechanism and the potential application prospects, aiming to provide novel ideas for future basic research and clinical applications.

Objective:To observe any influence of combining proprioceptive training with core stability training in rehabilitation motor functioning and balance after extensive burns.Methods:Sixty patients with lower limb motor and balance disorders after extensive burns were randomly divided into a treatment group and a control group, each of 30. Both groups underwent skin grafting on the lower limbs. After the wounds had healed, both groups were given routine rehabilitation treatment, including joint stretching and muscle strength training, but the treatment group was additionally provided with proprioception and core stability training. Before and after 12 weeks of treatment, both groups′ lower limb motor function and walking ability were evaluated using the Fugl-Meyer Assessment (L-FMA), and static and dynamic balance were quantified using Holden Functional Ambulation Classification (FAC). The duration of standing on one leg with the eyes closed was recorded, along with Timed " Up & Go" Test (TUGT) times. After the treatment, each patient′s satisfaction was assessed using a self-designed questionnaire.Results:Significant improvement was observed in the average L- FMA and FAC scores after the treatment, as well as in the ability to stand on one leg with the eyes closed. The average TUGT time in both groups was shorter, but there had been significantly greater improvement of the treatment group than among the controls. Reported satisfaction was significantly higher among the treated group than among the controls.Conclusions:Supplementing basic rehabilitation with proprioception training and core stability training can further improve the motor functioning, balance and walking of persons who have suffered extensive burns.

Objective:To explore the effect of self-made static progressive braces in the stepwise treatment of hand flexion dysfunction caused by scar contracture after burn injury.Methods:This study was a retrospective observational study. From January 2022 to March 2024, the First Affiliated Hospital of Air Force Medical University admitted twenty-nine patients who met the inclusion criteria and used the self-made static progressive braces for stepwise treatment of hand flexion dysfunction caused by scar contracture, including 23 males and 6 females, aged 16 to 55 years. The depth of burn on the back of the hand was deep partial-thickness to full-thickness. The self-made static progressive brace referred to the self-made static progressive joint distractor and the self-made static progressive hand flexion distractor. The stepwise treatment was adopted. In the first stage, in-hospital treatment for 2 to 4 weeks was selected. The treatment contents included conventional rehabilitation training and training on the application of the self-made joint distractors. When the active flexion range of motion of the metacarpophalangeal joint was ≥60°, the second stage of treatment was carried out, that is, two weeks of home remote rehabilitation treatment. The treatment contents included individualized exercise training such as training with self-made static progressive joint distractors and training with self-made static progressive hand flexion distractors. Adverse events such as blister, brace compression, and tissue strain during the stepwise treatment were recorded. After the end of the stepwise treatment, the active flexion of the affected hand was observed. During follow-up, the total active range of motion of the affected hand was measured, and the extensibility of the scar and skin and soft tissue on the back of the affected hand and the patient's satisfaction with the therapeutic effect were evaluated. At the last follow-up, the function of the affected hand was evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association.Results:During the stepwise treatment, a small amount of blisters developed on the skin at the wrist joint in 2 patients, which was cured after symptomatic treatment; the other patients had no adverse events such as brace compression and tissue strain. After the end of the stepwise treatment, the active flexion function of the hand was better, and the fist could be basically clenched. After 1-3 months of follow-up, the total active range of motion of the affected hand was 200-245°; the scar on the back of the hand was soft and light-colored, and the skin and soft tissue was malleable. Twenty-two patients were very satisfied with the curative effect, 6 patients were satisfied, and 1 patient was dissatisfied. At the last follow-up, there were 20 cases with excellent hand function and 9 cases with good hand function.Conclusions:The stepwise treatment of hand flexion dysfunction caused by scar contracture after burn injury with self-made static progressive braces has a good effect and few complications. Moreover, the two self-made static progressive distractors are convenient in material acquisition, simple to make, cost-effective, and highly practical, which is worthy of clinical promotion.

Purpose To explore the changes of brain function and network in primary insomnia(PI)patients using the percent amplitude of fluctuation(perAF)combined with functional connectivity(FC).Materials and Methods A total of 51 PI patients and 45 normal controls underwent resting functional magnetic resonance scans in Kunshan Traditional Chinese Medicine Hospital from November 2019 to December 2022,then the perAF value and FC in brain regions of different perAF value between the two groups was analyzed.Pearson correlation analysis was used to investigate the relationships between the altered perAF values and insomnia years,Pittsburgh sleep quality index and Montreal cognitive assessment.Results Compared with healthy group,PI patients had increased perAF values in the left prefrontal lobe(-42 9 45)and decreased perAF values in the right parahippocampal gyrus(27-12-27)[Gaussian random field(GRF)correction,voxel-wise P<0.001,cluster-level P<0.05].FC analysis showed that the right parahippocampal gyrus of PI patients exhibited significantly increased FC with the left middle temporal gyrus,inferior temporal gyrus(-57-15-33)and the left middle occipital gyrus(-30-78 27)(GRF corrected,voxel-wise P<0.001,cluster-level P<0.05).It was noteworthy that the perAF values of the right parahippocampal gyrus were positively correlated with Montreal cognitive assessment of PI patients(r=0.428,P=0.002).Conclusion Specific brain areas in PI patients may exhibit aberrant neuronal activity,mainly manifested as decreased perAF value in the right parahippocampal gyrus,which was increased FC with the left middle temporal gyrus,inferior temporal gyrus and the left middle occipital gyrus.These discoveries may be the core of the mechanism of impaired brain function in PI patients.

Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.

Objective To explore the relationship between systemic immune-inflammation index(SⅡ)at admission and occurrence of early neurological deterioration(END)in patients with branch atheromatous disease(BAD).Methods A retrospective analysis was performed on 326 BAD patients admitted in Department of Neurology of Handan Central Hospital from October 2021 to February 2024.Based on occurrence of END or not,they were divided into END group(97 cases)and non-END group(229 cases).Clinical data of the patients were collected,and multivari-ate logistic regression analysis was used to identify the END risk variables in BAD patients.ROC curve was plotted to evaluate the value of NIHSS score,hs-CRP and SⅡ in predicting the inci-dence of END in the patients.Results Significantly advanced age,higher NIHSS score at admis-sion,and elevated hs-CRP level,neutrophil count and SⅡ,but lower platelet and lymphocyte counts were observed in the END group than the non-END group(P＜0.05,P＜0.01).Multi vari-ate logistic regression analysis indicated that NIHSS score at admission(OR=1.134,95％CI:1.050-1.226,P=0.001),hs-CRP(OR=1.131,95％CI:1.024-1.249,P=0.015),and SⅡ(OR=1.001,95％CI:1.001-1.002,P=0.003)were independent risk factors for END in BAD patients.The AUC value of SⅡ in the prediction of END was 0.660,which was significantly higher than that of NIHSS score and hs-CRP in BAD patients(P＜0.05).Conclusion SⅡ is an independent risk factor for END in BAD patients,and SⅡ at admission has a certain predictive value for the oc-currence of END in these patients.