Objective To investigate the regulatory effect of circular RNA ASAP1(circASAP1)targeting microRNA-4500(miR-4500)on the proliferation and apoptosis of osteosarcoma cells.Methods Human osteosarcoma cells(Saos-2)were selected as the experimental subjects and cul-tured in DMEM medium containing 10％fetal bovine serum while maintaining 5％CO2.The expres-sions of circASAP1 and miR-4500 in osteosarcoma tissues were detected using RT-qPCR.Saos-2 cells were transfected with si-NC(40 nmol/L),si-circASAP1(40 nmol/L),pcDNA(0.4 μg),pcDNA-circASAP1(0.4 μg),miR-NC(40 nmol/L),miR-4500 mimics(40 nmol/L),si-circASAP1+anti-miR-NC(40 nmol/L),and si-circASAP1+anti-miR-4500(40 nmol/L),respectively.Cell proliferation and apoptosis were assessed using CCK-8,colony formation assays,and flow cytometry.The interaction between circASAP1 and miR-4500 was analyzed using a dual-luciferase reporter assay.Results Compared with adjacent non-tumor tissues,the expression of circASAP1 was significantly upregulated,while that of miR-4500 was significantly downregulated in osteosarcoma tissues(P＜0.001).Compared with the si-NC group,the si-circASAP1 group exhibited significantly decreased circASAP1 expression,optical density(OD)values,and the number of cell colonies(P＜0.001).Compared with the si-NC group,the si-circASAP1 group showed significantly upregulated levels of cleaved-caspase3 protein,cleaved-caspase9 protein,and the apoptosis rate(P＜0.001).StarBase search revealed specific binding sequences between miR-4500 and circASAP1.Co-transfection of miR-4500 mimics and WT-circASAP1 significantly reduced the relative luciferase activity of the cells[(0.34±0.03)versus(0.95±0.06),t=27.280,P＜0.001].The expression of miR-4500 in the pcDNA-circASAP1 group was significantly lower than that in the pcDNA group,whereas the ex-pression of miR-4500 in the si-circASAP1 group was significantly higher than that in the si-NC group(P＜0.001).Compared with the miR-NC group,the miR-4500 group exhibited significantly in-creased miR-4500 expression,cleaved-caspase3 protein levels,cleaved-caspase9 protein levels,and the apoptosis rate,while the OD values and the number of colonies significantly decreased(P＜0.001).Compared with the si-circASAP1+anti-miR-NC group,the si-circASAP1+anti-miR-4500 group showed significantly decreased miR-4500 expression,cleaved-caspase3 protein levels,cleaved-caspase9 protein levels,and the apoptosis rate,while the OD values and the number of col-onies significantly increased(P＜0.001).Conclusion The expression of circASAP1 is increased,while that of miR-4500 is decreased in osteosarcoma tissues.Moreover,circASAP1 promotes the proliferation and inhibits the apoptosis of osteosarcoma cells by targeting miR-4500.

Objective To explore the risk factors for clinical severity in patients with hypertriglyceridemic acute pancreatitis(HTG-AP).Methods A retrospective cohort study was conducted to collect the clinical data of HTG-AP patients admitted to the First Hospital of Putian City from June 2022 to December 2023.Patients were divided into a non-severe group(132 cases)and a severe group(22 cases)according whether they developed complications such as organ dysfunction and pancreatitcs necrosis.The differences in baseline characteristics between the two groups were compared,such as general data[including gender,age,body mass index(BMI),history of hypertension and diabetes],laboratory examination indicators[including glycated hemoglobin(HbA1c),white blood cell count(WBC),C-reactive protein(CRP),procalcitonin(PCT),systemic immune-inflammation index(SII),serum albumin(Alb),serum mylase to serum calcium ration(ACR),D-dimer,platelet count(PLT),total cholesterol(TC),triglycerides(TG),high-density lipoprotein(HDL),and low-density lipoprotein(LDL)].Univariate and multivariate Logistic regression analyses were used to screen for independent risk factors for clinical severity in HTG-AP patients,and the predictive efficacy of various risk factors for clinical severe progression of HTG-AP was evaluated using the receiver operator characteristic curve(ROC curve).Results A total of 154 patients were included,including 131 males and 23 females;the age range was 18-67 years,average was(39.00±8.74)years.A total of 22 patients developed clinical severity,with an incidence rate of 14.3%.There were no statistically significant differences between the two groups in terms of gender,age,BMI,hypertension,diabetes,HbA1c,WBC,CRP,Alb,PLT,TC,TG,HDL,and LDL.Compared with the non-severe group,the levels of PCT,D-dimer,ACR,and SII were significantly higher in the severe group[PCT(μg/L):0.34(0.12,0.49)vs.0.09(0.05,0.35),D-dimer(μg/L):1 010(340,1 790)vs.310(200,700),ACR:201.10(121.71,568.53)vs.61.79(27.99,153.77),SII:2 076.57(1 187.06,3 665.47)vs.1 033.95(717.95,1 466.76),all P<0.05].Multivariate Logistic regression analysis showed that ACR at admission was an independent risk factors for the development of clinical severity in HTG-AP patients(P<0.05).ROC curve analysis indicated that ACR has certain value in predicting clinical severity in HTG-AP area under the curve(AUC)=0.787[95%confidence interval(95%CI)was 0.685-0.890],P<0.001,and when the optimal cut-off value was set at 79.663,its sensitivity was 90.9%and specificity was 58.3%.Conclusion An abnormally elevated ACR at admission in HTG-AP patients is significantly associated with the risk of clinical severity and can be used as potential predictive indicator for early identification of high-risk patients.

Vertebral refracture following percutaneous vertebral augmentation (PVA) is commonly seen in elderly patients with osteoporotic thoracolumbar compression fractures (OTLCF). It can lead to recurrent pain, loss of vertebral height, progression of kyphosis, and even neurological dysfunction, significantly impairing patients′ quality of life. Current diagnosis and treatment face multiple challenges, including high misdiagnosis rate, difficulty in choosing between surgical and non-surgical treatment options, lack of standardized surgical protocols, interference from intralesional bone cement during procedures, inadequate stability of internal fixation in osteoporotic bone, and suboptimal compliance of anti-osteoporotic therapy. Establishing a standardized diagnostic and therapeutic framework is urgently needed. To standardize the management process and improve outcomes for vertebral refractures after PVA in elderly OTLCF patients, Spinal Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field to develop Guideline for the diagnosis and treatment of vertebral refracture after percutaneous vertebral augmentation in elderly patients with osteoporotic thoracolumbar compression fractures ( version 2025), based on current literature and clinical experience, and adhering to principles of scientific rigor and clinical applicability. A total of 11 recommendations were proposed, encompassing diagnosis, treatment, and rehabilitation of vertebral refracture after PVA in elderly patients with OTLCF, aiming to provide a foundation for a standardized management.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

Objective:To investigate the clinical efficacy of lumbar lateral interbody fusion (LLIF) versus posterior lumbar interbody fusion (PLIF) in the treatment of severe lumbar spinal stenosis.Methods:The data of patients with severe lumbar spinal stenosis who underwent LLIF or PLIF from February 2019 to December 2023 were retrospectively analyzed. There were 30 patients in the LLIF group, 10 males and 20 females, aged 62.7±5.6 years (range, 53-74 years), including 21 cases of single segment and 9 cases of double segment. There were 46 patients in the PLIF group, including 20 males and 26 females, aged 63.2±8.4 years (range, 43-75 years), 40 cases of single segment and 6 cases of double segment. The visual analogue scale (VAS), Oswestry disability index (ODI), intervertebral space height, intervertebral foramen height and postoperative complications were compared between the two groups.Results:All patients were followed up for an average of 21.3±6.4 months (range, 12-32 months). The intraoperative blood loss in the LLIF group was 112.2±76.9 ml, which was significantly lower than 193.9±88.2 ml in the PLIF group ( P<0.05). The VAS scores of back pain and leg pain after operation were significantly lower than those before operation in the two groups ( P<0.05). There was no statistically significant difference between groups in back pain VAS scores at preoperative, 6 months postoperative, and final follow-up ( P>0.05); the back pain VAS score at 1 month postoperatively in the LLIF group was 1.6±1.2, which was less than 2.8±0.7 in the PLIF group ( P<0.05). There was no statistically significant difference between groups in leg pain VAS scores at preoperative, 1 month postoperative, and 6 months postoperative ( P>0.05); the leg pain VAS score at the final follow-up in the LLIF group was 1.2±1.5, which was smaller than 1.8±1.0 in the PLIF group ( P<0.05). The postoperative ODI was smaller than the preoperative one in both groups, and the difference was statistically significant ( P<0.05); the preoperative, 1-month postoperative, 6-month postoperative, and final follow-up ODIs in the LLIF group were 45.7%±16.0%, 17.9%±12.0%, 16.2%±11.6%, and 15.7%±11.7%, and those in the PLIF group were 47.9%±15.4%, 20.1%±9.3%, 16.9%±10.6%, and 14.6%±11.0% in the PLIF group, and the difference between the groups was not statistically significant ( P>0.05). The preoperative intervertebral space height in the LLIF group was 10.6±2.0 mm, which was smaller than that in the PLIF group 11.8±2.2 mm ( P<0.05). The intervertebral space heights in the immediate postoperative period and at the final follow-up were 13.3±2.3 mm and 12.3±2.2 mm in the LLIF group and 13.7±1.7 mm and 13.0±1.9 mm in the PLIF group ( P>0.05). The preoperative intervertebral foraminal height in the LLIF group was 18.0±3.2 mm, which was smaller than that of 19.7±2.4 mm in the PLIF group ( P<0.05); the intervertebral foraminal heights in the immediate postoperative period and at the final follow-up were 21.4±2.5 mm and 20.2±2.4 mm in the LLIF group, and in the PLIF group were 20.7±2.4 mm and 19.7±2.6 mm in the PLIF group ( P>0.05). In the LLIF group, 2 cases had femoral nerve injury and 2 cases had transient back pain after operation. There were 2 cases of cerebrospinal fluid leakage, 1 case of screw loosening, and 2 cases of deep vein thrombosis in the PLIF group. In the PLIF group, 2 patients underwent revision, including 1 case due to cage displacement and 1 case due to screw malposition. The fusion settling rate was 21% (8/39) in the LLIF group and 12% (6/52) in the PLIF group ( P>0.05). Conclusion:Both LLIF and PLIF can effectively restore the intervertebral height, improve the lumbar function and the symptoms of back and leg pain in the treatment of severe lumbar spinal stenosis.

Objective:To investigate the clinical efficacy of open arthrolysis in the treatment of posttraumatic elbow stiffness.Methods:A retrospective analysis was conducted on the data of 407 patients with post-traumatic elbow stiffness treated by open arthrolysis surgery in Shandong Provincial Hospital from January 2010 to January 2024. The cohort included 303 males and 104 females, with a mean age of 38.98±10.90 years (range, 18-72 years) and mean body mass index (BMI) of 24.32±3.29 kg/m 2 (range, 17.91-33.41 kg/m 2). There were 230 patients with right-sided elbow stiffness, 159 patients with left-sided elbow stiffness, and 18 patients with bilateral elbow stiffness. Initial injuries included 21 patients of isolated elbow dislocation; 25 patients of soft tissue injury; and 361 patients of initial intra-articular elbow fractures, among which there were 200 patients of multiple fractures, 87 patients of single distal humerus fracture, 43 patients of single proximal ulna fracture, and 31 patients of single radial head fracture. Initial injuries were treated non-surgically in 69 cases and surgically in 338 cases, among which 177 cases were retained with internal fixation. There were 334 preoperative patients complicated with heterotopic ossification and 73 patients without heterotopic ossification, with 99 patients undergoing early release (stiffness duration <6 months) and 308 patients undergoing late release (stiffness duration ≥6 months). Record the range of motion (ROM) of the elbow joint, forearm rotational range (FRR), visual analogue scale (VAS), Mayo elbow performance score (MEPS), modified Broberg-Morrey score (MBS), Oxford elbow score (OES), and disability of arm, shoulder and hand (DASH) score before and after surgery, and conduct comparative analysis. Results:All patients were followed up for an average of 41.86±10.27 months (range, 13-119 months). At 12 months postoperatively, elbow ROM improved from preoperative 33.7°±26.5° to 101.2°±24.0°, elbow FRR improved from preoperative 101.4°±53.5° to 138.9°±38.7°, the MEPS increased from 60.1±14.7 to 91.5±10.1, the BMS increased from 57.5±12.8 to 83.7±11.0, the OES decreased from 31.6±7.3 to 16.0± 4.6, the DASH score decreased from 38.8±13.9 to 10.1±9.5, and the VAS decreased from 3.0±2.3 to 0.9±1.1, with all changes showing statistical significance ( P<0.05). In patients with preoperative heterotopic ossification, postoperative mean flexion range was 120.1°±15.5° and elbow ROM was 102.6°±23.4°. In patients without preoperative heterotopic ossification, postoperative mean flexion range was 113.9°±15.6° and elbow ROM was 93.4°±26.4°. Statistically significant differences were observed between the two groups in postoperative flexion range and flexion-extension ROM. There were no statistically significant differences in the postoperative above-mentioned indicators between early and late release patients ( P>0.05). The supination range and elbow FRR in patients with multiple fractures were lower than those in patients with distal humerus fractures and proximal ulna fractures; the DASH score in patients with multiple fractures was higher than that in patients with proximal ulna fractures and radial head fractures; the OES score in patients with multiple fractures was higher than that in patients with proximal ulna fractures, and all differences were statistically significant ( P<0.05). Among 407 patients, complications included new-onset postoperative ulnar neuropathy in 61 cases, new heterotopic ossification in 11 cases, recurrent heterotopic ossification in 96 cases, elbow instability in 6 cases, and superficial surgical site infection in 2 cases. Conclusions:Open arthrolysis is an effective treatment option for post-traumatic elbow stiffness. Patients with preoperative heterotopic ossification have a greater postoperative flexion range and elbow flexion-extension range of motion. The surgical timing exerts no significant influence on the ultimate functional outcome of treatment in patients with post-traumatic elbow stiffness. Patients with different initial fracture sites exhibited significant differences in postoperative functional outcomes, including supination, DASH scores, and OES.

Objective To analyze the relationship between umbilical cord blood chemokines regulated upon activation normal T cell expressed and secreted(RANTES),C-X-C motif chemokine ligand 12(CXCL12),C-X-C motif chemokine receptor 4(CXCR4)and neonatal septicemia inflammatory response and outcome.Meth-ods A total of 242 children with neonatal septicemia admitted to a hospital from January 2020 to January 2024 were selected as the study subjects,and were divided into non-critical group(101 cases),critical group(79 cases)and extremely critical group(62 cases)according to neonatal critical case score.According to the prognosis,the subjects were divided into good prognosis group and bad prognosis group.The levels of RAN-TES,CXCL12,CXCR4 and inflammatory factors[C-reactive protein(CRP),interleukin-6,IL-1β]in umbilical cord blood of each group were detected.The correlation between RANTES,CXCL12,CXCR4 and inflammato-ry factors in umbilical cord blood of neonatal septicemia was analyzed by Pearson correlation,and the influen-cing factors of poor prognosis of neonatal septicemia were analyzed by multivariate Logistic regression.Re-ceiver operating characteristic(ROC)curve was drawn to analyze the value of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting the poor prognosis of neonatal septicemia.Results The levels of RAN-TES,CXCL12,CXCR4,CRP,IL-6 and IL-1β in umbilical cord blood of extremely critical group were higher than those of critical group and non-critical group,and the differences were statistically significant(P＜0.05).The levels of RANTES,CXCL12 and CXCR4 in umbilical cord blood of neonatal septicemia were posi-tively correlated with CRP,IL-6 and IL-1β(P＜0.05).Multivariate Logistic regression analysis showed that extremely severe,early-onset septicemia,high RANTES,high CXCL12 and high CXCR4 were risk factors for poor prognosis of neonatal septicemia(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of umbilical cord blood RANTES,CXCL12 and CXCR4 in predicting poor prognosis of neonatal septicemia were 0.810,0.814 and 0.763,respectively,and the AUC of three indicators combined prediction was 0.914,which was higher than that of single prediction.Conclusion The increased levels of RANTES,CX-CL12 and CXCR4 in umbilical cord blood of neonatal septicemia are associated with inflammation,aggravation and poor prognosis,and the combination of RANTES,CXCL12 and CXCR4 can predict the risk of poor prog-nosis of neonatal septicemia.

Objective To observe the clinical efficacy and safety of Kangyan Jingfang in the treatment of post-operative cancer-related fatigue in Stage ⅡB-Ⅲ colorectal cancer.Methods A total of 66 patients with stage ⅡB-Ⅲ colorectal cancer who were diagnosed as cancer-related fatigue(CRF)based on TCM syndrome differentiation as spleen vacuity and essence depletion were divided into treatment group and control group randomly,with 33 cases in each group.The treatment group was treated with conventional symptomatic treatment combined with Kangyan Jingfang,and the control group was treated with conventional symptomatic treatment,the course of treatment was 60 days.The scores of cancer-related Fatigue(CFS),TCM syndrome accumulation scale,the revised Piper fatigue scale,Karnofsky performance status,hospital anxiety and depression scale(HAD),tumor markers(CEA,CA19-9,CA72-4,CA12-5,CA15-3,CA242,CA50,Septin9 gene methylation,etc.),immune function(CD3+T lymphocyte level,CD4+T lymphocyte level,CD8+T lymphocyte level and CD4+/CD8+ratio)and safety indexes(blood routine,liver and kidney function)were compared between the two groups in order to evaluate the clinical efficacy of Kangyan Jingfang on CRF.Results 60 cases were included in the observation finally,including 30 cases in each group.After treatment,the scores CFS,TCM syndrome accumulation scale,the revised Piper fatigue scale and HAD of two groups were decreased,but the treatment group before treatment showed a significant decrease in all indicators compared to the control group(P<0.05).The KPS score in the treatment group improved after treatment compared to the control group significantly(P<0.05).CEA,CA19-9 and the methylation of Septin9 gene were significantly decreased in the treatment group after treatment(P<0.05).CD3 and CD4 in treatment groups were higher than control group after treatment significantly(P<0.05).There were no significant abnormal changes in safety indexes before and after treatment(P>0.05).Conclusion Kangyan Jingfang can effectively improve the clinical symptoms of cancer-related fatigue in patients with stage ⅡB-Ⅲ colorectal cancer after surgery,reduce the physical and emotional suffering of patients,improve the quality of life,and enhance the immune function of the body.The efficacy is safe and reliable,and it has certain clinical application value.