1.Expression of proprotein convertase subtilisin/kexin type 9 in macrophage lipid accumulation microenvironment and its targeted intervention
He CHEN ; Man ZHANG ; Lixin WANG ; Yingshu SHANG ; Yanyu MEI ; Ting ZHOU
Journal of Clinical Medicine in Practice 2025;29(11):33-41
Objective Low-density lipoprotein cholesterol(LDL-C)is causally associated with atherosclerotic cardiovascular disease(ASCVD).Proprotein convertase subtilisin/kexin type 9(PCSK9)increases the degradation of low-density lipoprotein receptor(LDL-R),thereby promoting lipid accumulation.This study investigated the mechanism of microRNA(miRNA)-125a-5p in regulating PCSK9 transcriptional expression and lipid accumulation through histone deacetylase sirtuin 6(SIRT6)-mediated histone acetylation.Methods RAW264.7 macrophages exposed to oxidized low-density lipoprotein(ox-LDL)were used to establish a macrophage lipid accumulation model.The cells were divided into eight groups:control group(Group A),ox-LDL group(Group B),SIRT6 agonist group(Group C),si-SIRT6 group(Group D),miR-125a-5p mimic group(Group E),miR-125a-5p mimic negative control group(Group F),miR-125a-5p inhibitor group(Group G),and miR-125a-5p inhibitor negative control group(Group H).Oil red O staining was used to verify lipid ac-cumulation in macrophages.Real-time fluorescent quantitative polymerase chain reaction(PCR)was employed to detect the gene expression levels of miR-125a-5p,SIRT6 and PCSK9.Western blotting was used to detect the protein expression levels of SIRT6,histone 3 lysine 9 acetylation(H3K9ac),histone 3(H3),and PCSK9.An LDL-C kit was used to measure cellular LDL-C con-tent.Results Compared with Group A,Group B exhibited increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3 rati-o,increased relative gene and protein expression of PCSK9,and elevated LDL-C levels,with statis-tically significant differences(P<0.01).In Group B,a positive correlation was observed between H3K9ac and PCSK9 protein expression(r=0.935 0,P<0.01),as well as between PCSK9 and LDL-C(r=0.981 3,P<0.01).Compared with Group B,Group C showed no significant change in miR-125a-5p expression(P>0.05),but increased relative SIRT6 gene and its protein expres-sion,decreased H3K9ac/H3 ratio,decreased relative gene and protein expression of PCSK9,and reduced LDL-C levels(P<0.01).In contrast,Group D,compared with Group B,had no signifi-cant change in miR-125a-5p gene expression(P>0.05),but decreased relative gene and protein expression of SIRT6,increased H3K9ac/H3 ratio,increased relative PCSK9 gene and its protein expression,and elevated LDL-C levels(P<0.05 or P<0.01).Group E,compared with Group B,showed increased relative gene expression of miR-125a-5p,decreased relative SIRT6 gene and its protein expression,increased H3K9ac/H3,increased relative PCSK9 gene and its protein ex-pression,and elevated LDL-C levels(P<0.01).Group G,compared with Group B,had de-creased relative gene expression of miR-125a-5p,increased relative gene and protein expression of SIRT6,decreased H3K9ac/H3 ratio,decreased relative PCSK9 gene and protein expression,and reduced LDL-C levels(P<0.01).No significant changes were observed in miR-125a-5p,SIRT6,H3K9ac/H3 ratio,PCSK9,or LDL-C levels in Groups F and H compared with Group B(P>0.05).Conclusion Epigenetics is an important regulatory mechanism in the development of ather-osclerosis(AS).Elevated LDL-C is a significant risk factor for AS,and increased PCSK9 expres-sion exacerbates lipid accumulation.Imbalance in histone acetylation is a novel mechanism involved in PCSK9-mediated lipid accumulation,potentially serving as an early detection marker for lipid me-tabolism disorders.SIRT6 acts as a protective factor by reversibly regulating PCSK9 transcriptional expression,reducing lipid accumulation,and delaying AS progression.MiR-125a-5p,as an up-stream regulatory gene of SIRT6,targets and inhibits SIRT6 transcription,thereby modulating his-tone acetylation,and may serve as a new target for early screening and prevention of dyslipidemia.
2.Systemic Lupus Erythematosus as a Dominant Disease in Traditional Chinese Medicine
Zihan WANG ; Yanyu CHEN ; Yong CUI ; Qingwen TAO ; Mei MO ; Ke XUE ; Xiaoxiao ZHANG ; Yuan XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):263-269
Systemic lupus erythematosus (SLE), a refractory autoimmune disease, is among the dominant diseases where traditional Chinese medicine (TCM) shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46th Youth Salon on Dominant Diseases (Systemic Lupus Erythematosus)" organized by the China Association of Chinese Medicine, which led to a consensus on "the advantages, challenges, interdisciplinary approaches, and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges, such as frequent misdiagnosis and missed diagnosis in the early stages, difficulty in achieving treatment targets, multiple side effects from pharmacotherapy, and the lack of management strategies for special populations, all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema, aversion to cold and cold limbs, fatigue, dry mouth, restlessness, and heat sensation in the palms and soles, thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine, slow disease progression, reduce relapse rates, address multi-organ involvement, and prevent or treat complications. Additionally, they enhance efficacy and reduce toxicity, prevent the side effects of Western medications, help reduce hormone use, and offer distinct advantages in the individualized intervention of special populations, contributing to the whole-process management of the disease. However, evidence-based medical support for this integrated approach remains limited, and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research, strengthen the development of fundamental and pharmacological research, and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine, incorporating multi-omics technologies, individualized stratification, and other precision medicine concepts, in combination with artificial intelligence. Moreover, interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae, thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.
3.Systemic Lupus Erythematosus as a Dominant Disease in Traditional Chinese Medicine
Zihan WANG ; Yanyu CHEN ; Yong CUI ; Qingwen TAO ; Mei MO ; Ke XUE ; Xiaoxiao ZHANG ; Yuan XU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):263-269
Systemic lupus erythematosus (SLE), a refractory autoimmune disease, is among the dominant diseases where traditional Chinese medicine (TCM) shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46th Youth Salon on Dominant Diseases (Systemic Lupus Erythematosus)" organized by the China Association of Chinese Medicine, which led to a consensus on "the advantages, challenges, interdisciplinary approaches, and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges, such as frequent misdiagnosis and missed diagnosis in the early stages, difficulty in achieving treatment targets, multiple side effects from pharmacotherapy, and the lack of management strategies for special populations, all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema, aversion to cold and cold limbs, fatigue, dry mouth, restlessness, and heat sensation in the palms and soles, thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine, slow disease progression, reduce relapse rates, address multi-organ involvement, and prevent or treat complications. Additionally, they enhance efficacy and reduce toxicity, prevent the side effects of Western medications, help reduce hormone use, and offer distinct advantages in the individualized intervention of special populations, contributing to the whole-process management of the disease. However, evidence-based medical support for this integrated approach remains limited, and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research, strengthen the development of fundamental and pharmacological research, and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine, incorporating multi-omics technologies, individualized stratification, and other precision medicine concepts, in combination with artificial intelligence. Moreover, interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae, thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.
4.Stage Ⅲ Kümmell's disease treated with injured-vertebra screw placement combined with transpedicular impaction bone grafting:quick restoration of spinal stability
Xuejing ZHENG ; Wei MEI ; Yanyu ZHU ; Xiaoxiao BAO ; Zhenhui ZHANG ; Qingde WANG
Chinese Journal of Tissue Engineering Research 2024;28(18):2865-2870
BACKGROUND:Stage Ⅲ Kümmell's disease is characterized by a high degree of vertebral compression and posterior wall defects.Most of the patients are elderly people with severe osteoporosis and various medical diseases.Clinically,some surgical methods are often at high risk and are controversial. OBJECTIVE:To investigate the clinical efficacy of screw placement combined with transpedicular impaction bone grafting in the treatment of stage Ⅲ Kümmell's disease. METHODS:The clinical data of injured vertebral screw placement combined with transpedicular impaction bone grafting in treatment of stage Ⅲ Kummell's disease from May 2016 to August 2021 were retrospectively analyzed.Visual analog scale score,Oswestry disability index,anterior vertebral heights,kyphotic Cobb angle and American Spinal Injury Association(ASIA)impairment scale were used to evaluate the effects of surgery.The operation time,intraoperative blood loss and complications were recorded.CT scans were used to evaluate the healing of injured vertebrae at the final follow-up visit. RESULTS AND CONCLUSION:(1)A total of 26 patients were included,with 7 males and 19 females,at the age range of 62-81 years[mean(69.7±4.8)years].The follow-up time was 18-60 months[mean(35.1±8.9)months].The average operative duration was 133.5 minutes(100-165 minutes),and the average intraoperative blood loss was 285.3 mL(210-350 mL).(2)Visual analog scale and Oswestry disability index scores 1 week after surgery were significantly lower than those before surgery.(3)At 1 week after surgery,the anterior vertebral height corrections and the Cobb angle were(9.0±0.7)mm and(16.2±1.0)°,respectively.During the follow-up period,the loss of vertebral height and kyphosis correction were(5.1±0.3)mm and(8.0±0.4)°,respectively.(4)14 patients(54%)had ASIA grade D before operation,which recovered to grade E at the last follow-up.CT scan showed that all patients achieved good osseous union.(5)Complications occurred in seven patients(27%),including hypostatic pneumonia in two cases,postoperative superficial wound tissue liquefaction in two cases,and adjacent vertebral compression fractures in three cases.(6)It is concluded that screw placement of the injured vertebra combined with transpedicular impaction bone grafting can rapidly rebuild spinal stability,effectively relieve pain and improve neurological function in the treatment of stage Ⅲ Kümmell's disease.This technique is an effective and relatively minimally invasive surgical option.
5.Posterior long segment instrumentation combined with transpedicular impaction bone grafting or with bone cement augmentation in the treatment of stage III Kümmell disease: a comparison of efficacies
Wentao JIANG ; Wei MEI ; Qingde WANG ; Yanyu ZHU ; Zhenhui ZHANG ; Peilin LIU ; Kai SU ; Yongsheng KANG
Chinese Journal of Trauma 2023;39(7):611-618
Objective:To compare the efficacies of posterior long segment instrumentation combined with transpedicular impaction bone grafting or with bone cement augmentation in treating stage III Kümmell disease.Methods:A retrospective cohort study was conducted to analyze the clinical data of 38 patients with stage III Kümmell disease who were admitted to Zhengzhou Orthopedic Hospital between January 2016 and December 2020. The study included 8 male and 30 female patients, with ages ranging from 59 to 81 years [(68.9±4.9)years]. The vertebral fractures occurred at T 8 in 1 patient, T 11 in 9 patients, T 12 in 10 patients, and L 2 in 10 patients. Seventeen patients underwent posterior long segment instrumentation combined with transpedicular impaction bone grafting (impaction bone grafting group), and 21 patients underwent posterior long segment instrumentation combined with bone cement augmentation (bone cement group). The surgical duration, intraoperative blood loss, and incidences of postoperative complications were compared between the two groups. Additionally, the visual analogue score (VAS), Japanese orthopedic association (JOA) score, and Cobb angle were compared before the operation, at 1 week and 3 months post-operation, and at the final follow-up for both groups. The study also compared bone healing at the last follow-up and postoperative complication rates between the two groups. Results:All the patients were followed up for 24-35 months [(28.7±2.9)months]. The impaction bone grafting group had a surgical duration of (150.7±25.4)minutes and intraoperative blood loss of (285.3±48.6)ml, significantly different from those in the bone cement group [(132.0±21.1)minutes, (251.4±44.8)ml] (all P<0.05). Before the operation, there were no significant differences in the VAS, JOA score, or Cobb angle between the two groups (all P>0.05).The VAS was (3.2±0.8)points, (2.7±0.5)points and (2.2±0.7)points in the impaction bone grafting group and was (2.7±0.6)points, (2.6±0.7)points and (2.4±0.8)points in the bone cement group at 1 week and 3 months post-operation and at the final follow-up, respectively. The VAS in the impaction bone grafting group was significantly higher than that in the bone cement group at 1 week post-operation ( P<0.05); however, no significant differences were found at 3 months post-operation or at the last follow-up (all P>0.05). There was no significant difference in the JOA score between the two groups at 1 week or 3 months post-operation, or at the final follow-up (all P>0.05). The Cobb angle in the impaction bone grafting group was (5.1±1.3)°, (5.9±1.8)° and (6.5±2.5)° at 1 week and 3 months post-operation, and at the final follow-up, significantly lower than that in the bone cement group [(8.4±1.6)°, (12.6±2.1)°, and (14.5±3.3)°] (all P<0.01). All the patients in the impaction bone grafting group achieved bone healing at the last follow-up. One patient in the impaction bone grafting group experienced delayed incision healing, whereas two patients in the bone cement group had poor bone healing. The complication rate was 5.9% (1/17) in the impaction bone grafting group and 9.5% (2/21) in the bone cement group ( P>0.05). Conclusions:Posterior long segment instrumentation combined with transpedicular impaction bone grafting or with bone cement augmentation are both effective in alleviating pain and improving the spinal function for stage III Kümmell disease. The former procedure is associated with longer surgical duration and increased intraoperative blood loss, but it can provide superior correction and maintenance of kyphosis deformity, promoting the healing of the injured vertebrae.
6.Effect of different partial pressure of oxygen on the clinical outcome of pulmonary hypertension induced by meconium aspiration syndrome
Shaodong HUA ; Ming CHI ; Chong CHEN ; Yanyu FAN ; Yabo MEI ; Zhichun FENG
Chinese Pediatric Emergency Medicine 2019;26(1):51-55
Objective To study the role of partial pressure of oxygen in the treatment of pulmonary hypertension induced by meconium aspiration syndrome. Methods Retrospective analysis was performed on 58 patients with meconium aspirate and pulmonary hypertension from January 1,2007 to December 31,2016, 28 patients in the death group,and 30 patients in the survival group. Blood gas analysis about two groups of children with mechanical ventilation were collected at four different time points:before mechanical ventilation ( 0 h) ,12 hours after mechanical ventilation,24 hours after mechanical ventilation and 72 hours after mechan-ical ventilation. The 80 mmHg(1 mmHg=0. 133 kPa) in blood gas analysis of the partial pressure of oxygen was used as the boundary point to study the effects about different blood oxygen partial pressures on the length of mechanical ventilation time in the survival group. Results Blood gas analysis showed that there were no significant differences in pH,partial pressure of oxygen,HCO3-,and lactic acid before mechanical ventilation in the two groups,but the pH values were significantly higher in the survival group after 12 h, 24 h,and 72 h of mechanical ventilation(t values:-2. 07,-3. 48,-7. 11;P <0. 05). Partial pressure of oxygen were higher in the surviving group at 12 h,24 h,and 72 h than those in the death group(t values-2. 87,-4. 88,-11. 29; P<0. 05). The HCO3-values of the survival group at 12 h,24 h and 72 h were higher than the death group, and the differences were statistically significant ( t values: -3. 90, -5. 60,-5. 76,P<0. 001). The lactic acid of survival group was significantly lower than the death group at 72 h after ventilation (t=5. 12,P<0. 001). Compared with the death group,partial pressure of carbon dioxide in 24 h,72 h decreased significantly in the surviving group(t values:5. 67,7. 60;P<0. 05). In the surviving group,the partial pressure of oxygen was maintained above 80 mmHg in 18 patients and the mechanical venti-lation time was (7. 17 ± 1. 95) d. The partial pressure of oxygen was below 80 mmHg in 12 patients of the surviving group and the mechanical ventilation time was (8. 67 ± 2. 50)d. The difference was statistically sig-nificant(t =12. 02,P <0. 001). Conclusion In the treatment of newborn with pulmonary hypertension caused by meconium aspiration,maintaining a higher pH value and a partial pressure of oxygen higher than 80 mmHg may be beneficial to the recovery of children with pulmonary hypertension.

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