1.Mechanism of Modified Si Junzitang and Shashen Maidong Tang in Improving Sensitivity of Cisplatin in EGFR-TKI Resistant Lung Adenocarcinoma Cells Based on Aerobic Glycolysis
Yanping WEN ; Yi JIANG ; Liping SHEN ; Haiwei XIAO ; Xiaofeng YANG ; Surui YUAN ; Lingshuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):39-46
ObjectiveTo investigate the mechanism of modified Si Junzitang and Shashen Maidong Tang [Yiqi Yangyin Jiedu prescription (YQYYJD)] in enhancing the sensitivity of cisplatin in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant lung adenocarcinoma cells based on aerobic glycolysis. MethodsThe effects of different concentrations of YQYYJD (0, 2, 3, 4, 5, 6, 7, 8 g·L-1) and cisplatin (0, 3, 6, 9, 12, 15, 18, 21, 24, 27 mg·L-1) on the proliferation and activity of PC9/GR cells were detected by the cell counting kit-8 (CCK-8) assay after 24 hours of intervention. The half-maximal inhibitory concentration (IC50) for PC9/GR cells was calculated to determine the concentrations used in subsequent experiments. PC9/GR cells were divided into blank group (complete medium), YQYYJD group (5 g·L-1), cisplatin group (12 mg·L-1), and combined group (YQYYJD 5 g·L-1 + cisplatin 12 mg·L-1). After 24 hours of intervention, cell viability was measured using CCK-8 assay. Cell proliferation was assessed by colony formation assay, and cell migration was evaluated by scratch and Transwell assays. Glucose consumption, lactate production, and adenosine triphosphate (ATP) levels were measured by colorimetric assays. The expression levels of glycolysis-related proteins, including hexokinase 2 (HK2), phosphofructokinase P (PFKP), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), glucose transporter 1 (GLUT1), and monocarboxylate transporter 4 (MCT4), were determined by Western blot. ResultsBoth YQYYJD and cisplatin inhibited the viability of PC9/GR cells in a concentration-dependent manner. The IC50 of PC9/GR cells for YQYYJD and cisplatin were 5.15 g·L-1 and 12.91 mg·L-1, respectively. In terms of cell proliferation, compared with the blank group, the cell survival rate and the number of colonies formed in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in cell survival rate and colony formation (P<0.01). In terms of cell migration, compared with the blank group, the cell migration rate and the number of cells passing through the Transwell membrane in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group exhibited a further significant reduction in cell migration rate and the number of cells passing through the Transwell membrane (P<0.01). In terms of glycolysis, compared with the blank group, glucose consumption, lactate production, and ATP levels in the YQYYJD group, cisplatin group, and combined group were significantly decreased (P<0.01). Compared with the YQYYJD and cisplatin groups, the combined group showed a further significant reduction in glucose consumption, lactate production, and ATP levels (P<0.05). Compared with the blank group, the protein expression levels of HK2, PFKP, PKM2, and LDHA in the YQYYJD, cisplatin, and combined groups were significantly decreased (P<0.01). The combined group showed a further significant reduction in the expression levels of these proteins compared with the YQYYJD and cisplatin groups (P<0.01). No significant differences were observed in the protein expression levels of GLUT1 and MCT4 among the groups. ConclusionYQYYJD can synergistically inhibit the proliferation and migration of PC9/GR cells and enhance their sensitivity to cisplatin. The mechanism may be related to the downregulation of the expression of glycolysis-related rate-limiting enzymes, including HK2, PFKP, PKM2, and LDHA, thereby inhibiting glycolysis.
2.Finite element modal analysis of whole spine in adolescent idiopathic scoliosis
Yufang ZHANG ; Shuai LI ; Ning LIU ; Haiwei GUO ; Xiaohua QI ; Meng LYU
Chinese Journal of Tissue Engineering Research 2024;28(30):4783-4787
BACKGROUND:Vibration environment can cause spinal injury,especially in patients with scoliosis.At present,there is no information about the inherent mode of the whole spine from T1 to the pelvis in scoliosis patients in the free state. OBJECTIVE:To analyze the dynamic characteristics of the whole spine in patients with scoliosis by the finite element method. METHODS:Based on CT scan images,a three-dimensional finite element model of the T1-pelvic total spine of an 11-year-old patient with thoracolumbar biflexion scoliosis was established,and the Cobb angles of thoracolumbar scoliosis were 36° and 24°,respectively.The mode analysis in the free state of the whole spine was carried out by the finite element method. RESULTS AND CONCLUSION:The fifteen-order free modes of the spine were extracted,and the dynamic characteristics of the scolio-curved spine were obtained.The resonance frequency distribution of the spine was concentrated.The thoracic vertebra was the most deformed in the whole spine model,and the amplitude of the thoracic vertebra was larger than that of the lumbar vertebra.Modal analysis was used to analyze the vibration characteristics of scoliosis patients in the vibration environment.It is of great significance to determine the natural frequency,vibration mode,and amplitude of scoliosis patients for analyzing the vibration characteristics of scoliosis.
3.Osteoporotic vertebral compression fracture predicted by functional cross-sectional area of paravertebral muscles
Wensheng ZHANG ; Zhenjie SONG ; Haiwei GUO ; Chunfei WU ; Handi YANG ; Ying LI ; Wenchao LI ; Hongjiang LIU ; Xiaoguang YANG ; Chao YUAN
Chinese Journal of Tissue Engineering Research 2024;33(33):5315-5319
BACKGROUND:Osteoporosis vertebral compression fracture is a common fracture secondary to osteoporosis,and there is currently a lack of effective predictive indicators and methods for osteoporosis vertebral compression fracture. OBJECTIVE:To investigate the predictive effects of paravertebral muscle degeneration,functional cross-sectional area,and percentage of fat infiltration on osteoporotic vertebral compression fractures. METHODS:The 224 patients with osteoporosis diagnosed from January 2018 to June 2022 were included.They were followed up for more than 2 years.They were divided into fracture group and non-fracture group according to the presence and absence of vertebral fracture.The detailed information of demographics,body mass index,bone mineral density and so on were collected.The functional cross-sectional area and percentage of fat infiltration of bilateral Psoas major muscle and extensor dorsi(Erector spinae muscles muscle and multifidus muscle)at the level of lower endplate of L2 vertebral body were measured and calculated. RESULTS AND CONCLUSION:(1)224 patients were ultimately included,of which 126 had fractures as the fracture group and 98 had no fractures as the non-fracture group.There was no statistically significant difference in age,gender,height,body mass,body mass index,and fracture segment between the two groups(P>0.05).(2)The bone mineral density of the fracture group was significantly lower than that of the non-fracture group(P<0.05).Functional cross-sectional areas of Psoas major muscle and extensor dorsi in the fracture group were significantly lower than those in the non-fracture group(P<0.05).The percentage of fat infiltration of the extensor dorsi in the fracture group was significantly higher than that in the non-fracture group(P<0.05).There was no significant difference in percentage of fat infiltration of Psoas major muscle between the two groups(P>0.05).(3)Receiver operating characteristic analysis showed that the vertebral bone mineral density,percentage of fat infiltration of extensor dorsi,functional cross-sectional area of extensor dorsi and percentage of fat infiltration of Psoas major muscle were 0.903 g/cm2,35.426%,418.875 mm2,and 6.375%,respectively.The areas under curve were 0.634,0.755,0.876,and 0.585,respectively.(4)These findings indicate that paravertebral muscle degeneration is strongly associated with the occurrence of osteoporotic vertebral compression fractures.The functional cross-sectional area of extensor dorsi muscle can effectively predict the occurrence of osteoporotic vertebral compression fractures,which is helpful for early prevention and treatment of osteoporotic vertebral compression fractures.
4.The current status of health literacy among caregivers of patients with liver cancer and analysis of its influencing factors
Yanfang LIU ; Lingmei ZHU ; Haiwei LIU ; Yaqin WU
Journal of Interventional Radiology 2024;33(2):191-196
Objective To understand the current status of health literacy among caregivers of patients with liver cancer and its influencing factors so as to provide a basis for improving the level of health literacy among caregivers of patients with liver cancer.Methods Using convenience sampling method,the caregivers of the liver cancer patients,who were admitted to the Department of Interventional Radiology of a certain grade ⅢA hospital in Changsha City,Hunan Province of China between April and October of 2022 and who met the inclusion and exclusion criteria,were selected as the research objects.The general information questionnaire,Health Literacy of Caregivers Scale-Cancer(HLCS-C),and Simplified Coping Style Questionnaire(SCSQ)were used to conduct the survey.Multiple linear regression analysis was used to analyze the factors influencing the health literacy among caregivers of patients with liver cancer.Results A total of 204 valid questionnaires were collected.The score of health literacy of caregivers was(123.08±16.66)points.The results of multiple linear regression analysis showed that the residence location,the monthly income per capita of the family,the number of hospitalization times,the length of care,work/study status,and coping style were the main factors influencing the health literacy(P<0.001),which explained 81.9%of the total variance.Conclusion The health literacy among the caregivers of patients with liver cancer is at a moderate level.Clinical medical staff can implement individualized health education by evaluating caregivers with different characteristics,encourage caregivers to seek and grasp disease-related information,and help the caregivers to adopt positive coping styles,so as to improve their health literacy.
5.Identification of key ferroptosis genes in paraspinal muscle degeneration based on RNA sequencing and bioinformatics analysis
Chunhong ZHANG ; Hongchao HUANG ; Yue LIU ; Lilong DU ; Haiwei XU ; Ning LI ; Yongjin LI
Tianjin Medical Journal 2024;52(9):991-995
Objective To explore the gene expression profile in paraspinal muscle degeneration(PMD)and identify key ferroptosis genes.Methods RNA sequencing was performed on paraspinal muscle tissue of 3 normal and 3 PMD patients respectively to obtain differentially expressed genes.Through protein-protein interaction(PPI)and gene functional enrichment analysis,the intersection of ferroptosis genes was identified to identify key hub genes associated with ferroptosis.The diagnostic value for PMD disease was analyzed by receiver operating characteristic(ROC)curves.Results A total of 292 differentially expressed genes were identified in PMD.Among them,125 genes were significantly downregulated and 167 genes were significantly upregulated.Bioinformatics analysis revealed that 14 differentially expressed genes were associated with ferroptosis.Among them,ferroptosis genes MUC1,ATF3 and CDKN1A were key hub genes with good specificity and sensitivity for diagnosing PMD.Functional enrichment analysis revealed that they may mediate the occurrence and progression of PMD by regulating cell apoptosis,ferroptosis and skeletal muscle tissue development and differentiation.Conclusion Ferroptosis genes MUC1,ATF3 and CDKN1A can serve as biomarkers for diagnosing PMD,providing theoretical basis for decoding the pathological mechanism of PMD and developing new drugs.
6.Analysis of factors influencing the timing of laparoscopic operation in children with cryptorchidism
Haiwei LIN ; Haiyang LIU ; Chengliang LIU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(6):846-852
Objective:To investigate factors influencing the timing of laparoscopic surgery in children with cryptorchidism.Methods:A retrospective analysis was conducted on data from 150 children with cryptorchidism treated at Linyi Central Hospital between January 2020 and June 2023. The children were grouped based on the median age of those who underwent surgery, with 75 children in the low age group and 75 children in the high age group. The timing of operation for included children was analyzed. Univariate and multivariate analyses were performed to assess laparoscopic operation timing in children with cryptorchidism. A predictive model for laparoscopic operation timing was constructed, and its prediction efficiency was analyzed.Results:Univariate analysis revealed significant differences in family income level, medical expense payment method, parents' education level, and residence attributes among children who underwent surgery at different timings ( χ2=12.37, 21.70, 9.28, 9.52, 7.73, all P < 0.05). Multivariate analysis demonstrated that independent risk factors for delayed laparoscopic surgery in children with cryptorchidism included low family income, self-payment of medical expenses, low parents' education level, and rural residence ( OR = 0.31, 0.21, 0.08, 0.05, 0.12, 0.13, 0.14, 0.21, 0.42, all P < 0.05). Based on the results of the multivariate analysis, a nomogram risk model was constructed with a C-index of 0.713. This model utilized independent influencing factors and the prediction probability of the P-value to predict the timing of operation. The Yoden index values were 22.67%, 22.67%, 25.33%, 28.00%, 22.67%, and 60.00%, respectively. Conclusion:Children with cryptorchidism still experience delayed surgery, which is attributed to several factors. The prediction model constructed using these influencing factors demonstrates good prediction efficiency.
7.Factors affecting the occurrence of cryptorchidism in children and the timing of surgery
Haiwei LIN ; Haiyang LIU ; Chengliang LIU
Chinese Journal of Primary Medicine and Pharmacy 2024;31(7):1022-1026
Objective:To investigate the risk factors for occurrence of cryptorchidism in children and the timing of surgery.Methods:Ninety-six children with cryptorchidism who received treatment at Linyi Central Hospital between January 2018 and December 2022 (cryptorchidism group) and 60 healthy young children born during the same period (control group) were included in this study. The mothers and fathers of the children were surveyed, and the risk factors for the occurrence of cryptorchidism in children were statistically analyzed. Additionally, the factors that affect the timing of surgery for the children were also evaluated.Results:(1) Children with cryptorchidism typically exhibited poor testicular development and a soft texture. Of the cases studied, 83 (86.4%) had unilateral cryptorchidism, with the left side affected in 21 cases and the right side affected in 62 cases. Additionally, 13 cases (13.6%) exhibited bilateral cryptorchidism. The testicles were located in the inguinal region in 76 cases and in the abdominal cavity in 20 cases. In 79 cases, the cryptorchid was palpable, whereas in 17 cases, it was not. Upon admission, the children's serum luteinizing hormone levels were (1.83 ± 0.25) U/L, follicle-stimulating hormone levels were (1.12 ± 0.13) U/L, and testosterone levels were (0.77 ± 0.09) nmol/L. (2) Multivariate logistic analysis revealed that mother's smoking history, drinking history, occupational exposure to pesticides or diesel/gasoline, use of anti-infective drugs/antipyretic analgesics during early pregnancy, gestational diabetes, father's smoking history, and history of occupational exposure to pesticides were the independent risk factors for the occurrence of cryptorchidism in children (all P < 0.05). (3) Parental education level, family income, and the presence of combined penile malformations emerged as independent risk factors that influence the timing of surgery for cryptorchidism in children (all P < 0.05). Conclusion:The educational level, occupation, and early pregnancy medication history of parents are the primary risk factors influencing the occurrence of cryptorchidism in children. Therefore, it is crucial to enhance health education targeted at low-income and poorly-educated families to prevent surgical delays.
8.Mechanisms and Clinical Application of Common Oral Chinese Patent Medicines Against Non-small Cell Lung Cancer: A Review
Yanping WEN ; Haiwei XIAO ; Liping SHEN ; Xiaofeng YANG ; Juhua YIN ; Lingshuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):260-266
Lung cancer tops the disease list in the world due to the high incidence and mortality, and about 85% of lung cancer cases is non-small cell lung cancer (NSCLC). Most NSCLC patients are in the advanced stage at the time of diagnosis, with a low 5-year survival. Traditional Chinese medicine (TCM) plays a role in the comprehensive treatment of malignant tumors. Oral Chinese patent medicines, as an important part of TCM, have the advantages of stable preparations, mild taste, simple package, and accurate effective ingredients, which are different from decoctions. They have been widely used in the adjuvant treatment of NSCLC. In clinical practice, the combination of oral Chinese patent medicines with chemotherapy, targeted therapy, or radiotherapy, as well as the application of the oral Chinese patent medicines alone, can increase efficiency, reduce toxicity, prolong the survival time of patients, and improve the quality of life. The mechanisms of oral Chinese patent medicines in the treatment of NSCLC mainly include inhibiting the proliferation, invasion, and metastasis of lung cancer cells, promoting the apoptosis of lung cancer cells, inhibiting tumor neovascularization, reversing multidrug resistance, and regulating the immune functions, which reflects the multi-pathway and multi-target manner of TCM. The oral Chinese patent medicines commonly used in the clinical treatment of NSCLC include Jinfukang oral liquid, Shenyi capsules, Pingxiao capsules, Xiao'aiping tablets, Kanglaite capsules, compound Cantharis capsules, Huisheng oral liquid, Yangzheng Xiaoji capsules, Xihuang pills, Zilongjin tablets, and Cinobufagin capsules. There are many clinical and basic studies about the treatment of NSCLC with these medicines, while a systematic review remains to be carried out. Therefore, we systematically reviewed the mechanisms and clinical application of commonly used oral Chinese patent medicines in the adjuvant treatment of NSCLC, aiming to provide reference for follow-up research and clinical treatment.
9.Microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion for lumbar degenerative diseases
Haiwei XU ; Baoshan XU ; Yue LIU ; Ning LI ; Hongfeng JIANG ; Yongcheng HU ; Lilong DU ; Tao WANG ; Xinlong MA ; Kaihui ZHANG
Chinese Journal of Orthopaedics 2022;42(7):395-402
Objective:To evaluate the value and efficacy of microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion (ALDF) for lumbar degenerative diseases.Methods:Anterior lumbar distractors were designed to maintain the distraction of intervertebral space and expose the posterior edge of the intervertebral space. From June 2018 to December 2020, 41 cases of lumbar degenerative diseases were treated with this operation, including 19 men and 22 women, aged 29-71 years old (average 42.1 years old). All patients had intractable low back pain. Imaging examination showed lumbar disc degeneration with narrow intervertebral space, including disc herniation with Modic changes in 7 cases, spinal stenosis with instability in 16 cases and spondylolisthesis in 18 cases. The involved levels included L 2,3 in 1 case, L 3,4 in 3 cases, L 2-L 4 in 1 case, L 4,5 in 17 cases and L 5S 1 in 19 cases. An incision was taken that was pararectus for L 2-L 4 and transverse for L 4-S 1, with the intervertebral disc exposed via extraperitoneal approach. The intervertebral space was released and distracted after discectomy in intervertebral space, and self-made distractors were used to maintain the space. Under microscope, the herniation, posterior annulus and osteophyte were removed for sufficient decompression, with a suitable self-anchoring cage implanted into the intervertebral space. The visual analogue score (VAS), Oswestry dysfunction index (ODI), intervertebral space height, lordosis angle and spondylolisthesis rate were evaluated. Results:Operations were performed successfully in all the patients. The operation time was 70-120 min with an average of 90 min, and the intraoperative blood loss was 15-70 ml with an average of 30 ml. No severe complication such as nerve or blood vessel injury occurred. The patients were followed up for 12 to 36 months, with an average of 18 months. At the last follow-up, VAS decreased from 6.4±2.3 to 1.1±0.9, and ODI decreased from 44.9%±16.9% to 5.8%±4.7%. Intervertebral space height recovered from 7.2±2.8 mm to 12.1±2.1 mm and lordosis angle recovered from 6.9°±4.8° to 10.1°±4.6°. X-ray showed significant recovery of intervertebral space height, lordosis angle and spondylolisthesis rate, with obvious interbody fusion and no displacement of cage. For 18 patients of spondylolisthesis, the slippage recovered from 16.6%±9.3% to 7.6%±5.3%, with an average improvement of 54.2%.Conclusion:Microscope-assisted minimally invasive ALDF can provide sufficient decompression and zero-profile fusion for lumbar degenerative diseases with satisfactory results during short-term follow-up.
10.Repair of defects after lumbar discectomy with autologous bone marrow mesenchymal stem cells and annular suture
Baoshan XU ; Hao ZHANG ; Qiuming YUAN ; Ying ZHANG ; Yongcheng HU ; Kaihui ZHANG ; Lilong DU ; Ning LI ; Yue LIU ; Haiwei XU
Chinese Journal of Orthopaedics 2022;42(11):685-695
Objective:To evaluate the safety and validity of enriched autologous bone marrow mesenchymal stem cells (BMSCs) and annular suture for repairing defect after lumbar discectomy.Methods:Enrichment of autologous BMSCs: autologous bone marrow blood was collected from 5 patients undergoing lumbar surgery, and nucleated cells were enriched on gelatin sponge particles by selective cell retention technique. From October 2016 to March 2019, 109 patients with lumbar disc herniation underwent discectomy with mobile microendoscopic discectomy technique, including 61 males and 48 females, aged 24-59 years. Discectomy group: 26 cases received simple discectomy. Suture group: 39 cases received annular suture after discectomy. BMSCs+suture group: 44 cases received intradisc transplantation of gelatin sponge particles enriched with autologous BMSCs and annular suture after discectomy. The perioperative conditions were recorded, with visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pfirrmann grade of disc degeneration, disc height and degree of herniationevaluated after operation.Results:In enrichment test with flow cytometry, the enrichment multiple of nucleated cells and target cells was 6.4±0.9 and 4.2±0.6 respectively, and BMSCs grew well in vitro. The operation time was 35-55 mins. 7 cases in the suture group were transferred to the discectomy group and 10 cases in the BMSCs+suture group were transferred to BMSCs group due to unsuccessful suture. There were no significant differences in VAS, ODI, Pfirrmann grade of disc degeneration, disc height and degree of herniation among the groups. There was no significant difference in intraoperative bleeding, postoperative drainage and length of hospital stay. The incision was healed without redness and swelling. 18 patients were followed up for 6 months, and 91 cases were followed up for 1-3 years (25.0±5.6 months). There was no interbody fusion, heterotopic ossification or infection during follow-up. VAS and ODI decreased significantly after operation in all patients. At final follow-up, the VAS improvement rate of BMSCs+suture group (81.7%±7.9%) was higher than discectomy group (73.0%±8.9%), suture group (74.0%±6.9%) and BMSCs group (75.3%±8.4%); the ODI improvement rate of BMSCs+suture group (91.9%±8.8%) was higher than discectomy group (86.2%±8.1%) and suture group (86.4%±5.5%). According to MRI, the Pfirrmann grade of disc increased 0.7 in discectomy group, 0.6 in suture group, while it did not increased significantly in BMSCs+suture group and BMSCs group, and the progress of Pfirrmann grade in BMSCs+suture group and BMSCs group were lighter than discectomy group and suture group.The disc height decreased in each group, the loss rate of disc height in BMSCs+suture group (17.2%±4.3%) was less than discectomy group (29.3%± 6.3%) and suture group (20.6%±5.7%); and suture group was less than discectomy group. The degree of herniation was reduced by more than 50% in all groups, while 1 case in discectomy group had herniation without clinical symptoms.Conclusion:Autologous BMSCs and annulus suture are safe and effective in repairing the defect after lumbar discectomy, which may help to slow down the degeneration of intervertebral disc.

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