ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Objective To investigate the clinical effect of acupotomology combined with Bushenzhuanggu prescription in the treatment of residual lumbar pain after percutaneous kyphoplasty(PKP)for osteoporotic vertebral compression fractures.Methods A total of 77 patients with PKP postoperative residual lumbar pain admitted to the Department of Orthopedics,Ningbo Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University from January 2018 to December 2021 were randomly divided into control group and observation group.Patients in control group were treated with calcitriol soft capsules and calcium carbonate D3 tablets,and patients in observation group were treated with acupotomy combined with Bushenzhuanggu prescription.The pain degree,lumbar function and self-care ability of the two groups were compared.Results After treatment,the pain level,lumbar function,and self-care abilityof the two groups of patients improved compared to before treatment.Compared with control group,the visual analogue score(VAS)score and Oswestry disability index(ODI)index of observation group decreased more significantly,and the difference was statistically significant(P<0.05);The Barthel index of observation group increased more significantly in the early stage(3 days and 1 month after treatment),with a statistically significant difference(P<0.05).However,there was no statistically significant difference in Barthel index between the two groups at 3 months after treatment(P>0.05).Conclusion Acupotomy combined with Bushenzhuanggu prescription has satisfactory clinical efficacy in the treatment of residual lumbar pain after PKP operation of osteoporotic vertebral compression fracture.It can significantly reduce pain,improve lumbar function,shorten the improvement time of patients'self-care ability,improve patients'quality of life,and effectively promote patients'rapid recovery.

OBJECTIVE To study the difference of Huangqin decoction combined with Paeoniae Radix Alba(BS) and Paeoniae Radix Rubra(CS)'s effect on ulcerative colitis(UC) based on network pharmacological analysis and animal experiment. METHODS The active constituents of BS and CS were retrieved from TCMSP database and literature, and the potential target was predicted by Swiss Target Prediction. Ulcerative Colitis was used as key words to search disease targets in DisGenet, OMIM, and Genecard databases. The intersection target was obtained by Venny 2.1.0. Cytoscape 3.7.2 software was used to construct network of drug-consumption targets. The STRING platform was used for protein-protein interaction(PPI) network analysis, and Metascape database was applied for GO/WIKI analysis. A dextran sulfate sodium(DSS) induced UC mouse model was established to compare the anti-UC effects of Huangqing decoction combined with BS(HQT-BS) and CS(HQT-CS), respectively. RESULTS There were 7 active components of HQT-BS and 11 active components of HQT-CS in the treatment of ulcerative colitis, respectively, 5 of which were the same. There were 146 and 157 targets respectively, 106 of which were the same. The core targets of HQT-BS were SRC, HSP90AA1, and PIK3R1, while the core targets of HQT-CS were SRC, HSP90AA1, and STAT3. WIKI enrichment analysis showed that several signaling pathways were shared by both BS and CS, such as EGFR tyrosine kinase inhibitor resistance, Notch signaling pathway. EGF/EGFR signaling pathway was the specific pathway related to BS, while Nuclear receptors meta-pathway and Kit receptor signaling pathway were the specific pathways related to CS, respectively. Animal experiments showed that both HQT-BS and HQT-CS could significantly improve colon shortening and tissue pathological alternation induced by DSS. However, HQT-CS was more effective in reducing the expression of interleukin-6 and neurogenic locus notch homolog protein1. CONCLUSION Both HQT-BS and HQT-CS have anti-UC effect, and HQT-CS is the better one.

Objective To predict the micro-level energy release rate in the rat femoral cortical bone and investigate the variation in the micro-level energy release rate with age.Methods Based on previous experimental data and numerical simulation of fracture modes for cortical bone,load-displacement curves and fracture modes measured by simulation and experiment were compared,and the micro-level energy release rates of rat femoral cortical bone at different months were predicted by back-calculation.Results It was predicted that the micro-level energy release rate of rat femoral cortical bone at 1-,3-,5-,7-,9-,11-,and 15-month age was 0.08-0.12,0.12-0.14,0.15-0.19,0.25-0.28,0.23-0.25,0.19-0.22,and 0.13-0.16 N/mm,respectively.Conclusions The decrease in the microlevel energy release rate with increasing age led to a decreasing failure load,indicating that the microlevel energy release rate is one of the main factors determining fracture occurrence;however,no significant decrease was observed at the time of fracture,indicating that the microlevel energy release rate was not linearly proportional to the fracture time.These results can help explain the mechanism of cortical bone fractures at the clinical level.

Objective:To investigate the effect of Yiqi Dihuang Decoction assisting conventional western medicine therapy in the treatment of early diabetic nephropathy (DN) with deficiency of qi and yin.Methods:A total of 117 patients with early DN who met the inclusion criteria from June 2018 to December 2020 in Beijing Hospital of Traditional Chinese Medicine Shunyi Branch were divided into a control group of 58 patients and a treatment group of 59 patients according to the random number table method. The control group was treated with conventional western medicine therapy, and the treatment group was additionally treated with Yiqi Dihuang Decoction on the basis of the control group. Both groups were treated for 1 month. Serum levels of IL-1, macrophage scavenger receptor A (SR-A), TNF-α, C-C motif chemokine 2 (CCL2), GSH-Px and SOD were detected by ELISA before and after treatment. Cystatin C (Cys C) and SCr levels were detected by automatic biochemical analyzer. The urinary albumin was determined by radioimmunoassay, urinary creatinine determined by rate method, and urinary albumin/creatinine ratio (UACR) and glomerular filtration rate (eGFR) were calculated. The adverse events during treatment and clinical efficacy were evaluated.Results:The total effective rate was 94.92% (56/59) in the treatment group and 81.03% (47/58) in the control group, and the difference between the two groups was statistically significant ( χ2=5.35, P=0.021). After treatment, UACR [(92.28±15.42) mg/g vs. (108.42±20.76)mg/g, t=4.78], eGFR [(91.42±13.18) m·min -1·1.73m -2vs. (95.30±15.94) m·min -1·1.73m -2, t=2.02], SCr [(65.30±9.54) μmol/L vs. (70.18±12.53) μmol/L, t=5.42], Cys C [(0.65±0.12)mg/L vs. (1.07±0.26)mg/L, t=11.25] in the treatment group were significantly lower than those in the control group ( P<0.05). Serum SR-A [(37.18±6.10) μg/L vs. (51.51±7.12) μg/L, t=11.70], CCL2 [(13.12±1.63) μg/L vs. (19.68±2.90) μg/L, t=15.12], TNF-α [(20.57±3.50) ng/L vs. (29.68±4.17) ng/L, t=12.81], IL-1 [(8.47±0.97) ng/L vs. (13.12±1.57) ng/L, t=19.31] levels in the treatment group were significantly lower than those in the control group ( P<0.01); serum SOD [(24.09±3.12) mg/L vs. (18.72±2.76) mg/L, t=9.85] activity and GSH-Px [(231.57±25.38) mg/L vs. (174.58±22.96) mg/L, t=12.73] in the treatment group were significantly higher than those in the control group ( P<0.01). During the treatment period, the incidence of adverse events was 10.34% (6/58) in the control group and 6.78% (4/59) in the treatment group, and there was no significant difference between the two groups ( χ2=0.48, P=0.490). Conclusion:Yiqi Dihuang Decoction assisted with conventional western medicine can effectively improve the renal function of patients with early DN syndrome of qi and yin deficiency, inhibit the body's inflammatory response and oxidative stress response, and improve clinical efficacy.

OBJECTIVE To explore wheth er there is a relationship between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence. METHODS By searching for medical damage liability disputes related to off-label drug use up to 2021 on pkulaw.cn ，documents were extracted to record objective factors ，subjective factors and judgment results ；whether there was evidence-based evidence was judged according to Off-label Drug Use List and Evidence-based Evaluation Standards for Off-label Drug Use of Guangdong Pharmaceutical Association ；univariate analysis was adopted to test the relationship between the judgment results and evidence-based evidence. RESULTS A total of 57 cases were included. Cases mainly occurred in the eastern China （63.2％）and tertiary hospitals （64.9％），the main appraisal agency was the appraisal center or institute（61.4％），and the most common type of off-label drug use was overdose drug use （45.6％）. Among the judgment results ， 23 cases（40.4％）of off-label drug use had a causal relationship with medical damage ，most of the responsibility of doctors was secondary responsibility （28.1％），and the actual compensation amount of the most cases were less than 100，000 yuan（54.4％）. There were 25 cases（43.9％）with evidence-based evidence. Univariate analysis found that for off-label drug use the claim amount of the case with evidence-based evidence was significantly higher than that of the case without evidence-based evidence （P＝ 0.040），and there was no significant correlation between evidence-based evidence and the actual compensation amount of the case （P＝0.741），causality determination （P＝0.256），liability type （P＝0.598）or appraisal agency （P≥0.260）. CONCLUSIONS There is no significant correlation between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence ，indicating that there may be certain differences between judicial trials and medical science. The off-label drug use should be regulated by establishing a complete off-label drug use management system and standardizing informed consent procedure for off-label drug use. 1610307322@pku.edu.cn

Objective:To evaluate the detection of copy number variation (CNV) by chromosome microarray analysis (CMA) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT).Methods:A total of 1 929 fetuses who were ultrasonically found with CAKUT and underwent CMA from Guangdong Women and Children's Hospital and Health Institute were enrolled in this retrospective study from January 2016 to July 2020. These fetuses were divided into isolated CAKUT group ( n=1 567), CAKUT with soft markers group ( n=269), and CAKUT with other structural anomalies group ( n=93) for comparing the detection rate of pathogenic CNV using Chi-square test or Fisher exact test. Results:(1)The detection rate of all and pathogenic CNVs were 6.5%(125/1 929) and 4.8%(93/1 929), respectively. The total detection rate of CNV, clinically significant CNV and large chromosome structural variations in the CAKUT with other structural anomalies group were higher than those of the CAKUT with soft markers group and isolated CAKUT groups[31.2%(29/93), 11.5%(31/269) vs 4.2%(65/1 567), χ2=119.002; 18.3%(17/93), 9.0%(24/269) vs 3.6%(56/1 567), χ2=49.677; 9.7%(9/93), 2.2%(6/269) vs 0.3%(4/1 567), χ2=42.727; all P<0.001]. CAKUT with other structural anomalies group had a higher detection rate of pathogenic CNV (18.3%, 17/93) than the CAKUT with soft markers group (8.6%, 23/269) and the isolated CAKUT group [3.4%(53/1 567)] ( χ2=51.932, P<0.001). (2) The detection rate of pathogenic CNV was the highest in fetuses with enhanced renal echo (14.7%, 23/156), followed by renal enlargement (8.2%, 5/61), renal dysplasia (5.0%,13/261), polycystic renal dysplasia (5.0%, 13/261), and hydronephrosis (4.8%, 20/413). Fetuses with polycystic renal dysplasia, renal agenesis, fused kidney and hydronephrosis in the CAKUT with other structural anomalies group had a higher detection rate of pathogenic CNV than those in the isolated CAKUT group [3/9 vs 3.5%(8/230), 2/17 vs 1.3%(3/237), 1/8 vs 0.0%(0/59) and 3/18 vs 3.4%(12/344), all P<0.017]. The CAKUT with other structural anomalies group had a higher detection rate of pathogenic CNV than CAKUT with soft markers group in fetuses with enhanced renal echo [4/8 vs 12.8%(5/39), P<0.017]. (3) The top three microdeletion/microduplication syndrome were 17q12 microdeletion syndrome (36.6%, 34/93), 22q11.2 microdeletion syndrome (23.7%, 22/93), and 16p11.2 microdeletion syndrome (7.5%, 7/93) among those with pathogenic CNV. Conclusions:The risk of CNV in fetuses with isolated CAKUT, CAKUT with soft markers, and CAKUT with additional structural anomalies increased progressively. CMA might be a better choice in fetuses with hydronephrosis, enhanced renal echo, renal enlargement, renal hypoplasia, and multicystic renal dysplasia to improve the detection rate of CNV.

Objective:To explore the effect of traditional Chinese medicine fumigation and washing on the clinical indicators of elderly patients with distal radius fractures after small splint fixation.Methods:From November 2015 to November 2018, 180 elderly patients with fracture of the distal radius in Ningbo Hospital of Traditional Chinese Medicine were selected, and they were divided into control group and observation group according to the random digital table method, with 90 cases in each group.The two groups were given manual reduction and small splint fixation treatment, and the observation group was treated with traditional Chinese medicine fumigation on the basis of the control group therapy.The related inflammatory cytokines in patients plasma and serum viscosity(TNF-α, IL-1, IL-6) were detected, and the clinical curative effect and adverse reactions were observed.Results:Before treatment, there were no statistically significant differences in plasma viscosity and blood inflammatory factors(TNF-α, IL-1, IL-6) between the two groups( t=-0.171, -0.126, 0.483, 0.459, all P>0.05). After treatment, the above indicators in the two groups were significantly lower than those before treatment(observation group: t=38.970, 14.684, 72.258, 53.612; control group: t=20.098, 19.045, 33.962, 34.822, all P<0.05), which in the observation group were lower than those in the control group ( t=-30.239, -7.043, -31.815, -10.359, all P<0.05). The total effective rate of the observation group was 88.88%(80/90), which was higher than 71.11%(64/90) of the control group, the difference was statistically significant between the two groups(χ2=8.889, P<0.05). Conclusion:For the elderly patients with distal radius fracture, the combination of reduction and small splint fixation and fumigation with traditional Chinese medicine can significantly improve the hemorheology of the patients and reduce the contents of inflammatory factors in the body, with significant efficacy and no adverse reactions, which is worthy of clinical application.

Objective To investigate the correlation between tumor perfusion parameters and tumor volume and Child-Pugh classification in CT of hepatocellular carcinoma (HCC).Methods Fifty-six patients with hepatocellular carcinoma were selected to perform CT perfusion imaging.The parameters of the total tumor perfusion such as hepatic artery perfusion (HAP),portal vein perfusion (PVP)and hepatic perfusion index (HAPI)were calculated according to the degree of hepatic encephalopathy,albumin,bilirubin, clotting time,ascites for liver Child-Pugh classification.The relationship between the tumor or peritumoral perfusion parameters with tumor volume and Child-Pugh classification were analyzed.Results (1)There was no correlation between tumor or peritumoral perfusion with the tumor volume.(2)The difference of HAP,PVP and HAPI between the different Child-Pugh classification groups was statistically significant (P<0.000 1).(3)With the reduction of Child-Pugh classification,the tumor body HAP and HAPI values gradually decreased, while the PVP value increased gradually.Conclusion There is no correlation between the tumor volume of hepatocellular carcinoma with total tumor perfusion parameters.The differences in perfusion measurements between different Child-Pugh classification can intuitively and quantitatively reflect the reserve function of the liver.

Objective To observe the influence of Kuailvning capsule(KLN)and its drug serum on the concentration of Ca2 + in rat ventricular muscle cells.Methods SD rats were randomly divided into five groups:the control group,serum control group,KLN high -dose group,KLN medium -dose group and KLN low -dose group,six mice in each group.The rat ventricular myocytes were separated by enzymatic hydrolysis.The influence of KLN and its drug serum on the concentration of Ca2 + in rat ventricular muscle cells were observed by Fluo -3 /AMprobe.Results The mean fluorescence intensity of cytosolic Ca2 + in the KLN high -dose group,KLN medium -dose group and KLN low -dose group after 50s,100s,150s,200s,250s were [(18.75 ±1.55),(16.69 ±0.93),(17.76 ±1.26)], [(25.47 ±1.118),(17.86 ±1.49),(17.81 ±1.13)],[(29.05 ±1.31),(20.14 ±1.73),(18.26 ±1.37)], [(35.21 ±1.33),(23.19 ±0.97),(18.18 ±1.46)],[(41.08 ±1.21),(26.34 ±1.69),(17.91 ±1.01)], which were higher than those in the control group(F =5.556,7.007,8.816,10.208,12.232,all P <0.01 ).The mean fluorescence intensity of cytosolic Ca2 + in the KLN high -dose group after 50s,100s,150s,200s,250s were (17.85 ±1.69),(18.95 ±1.73),(21.85 ±1.39),(23.01 ±1.48),(24.07 ±1.42),which were higher than those in the serum control group(t =3.642,4.406,6.074,7.402,8.625,all P <0.01 ).The mean fluorescence intensity of cytosolic Ca2 + in the KLN medium -dose group after 100s,150s,200s,250s were (18.01 ±1.42), (18.76 ±1.22),(19.73 ±1.37),(21.04 ±1.16),which were higher than those in the serum control group(t =3.902,4.033,4.126,4.326,all P <0.01).There were no statistically significant difference between the KLN low -dose group and the serum control group(P >0.05).Conclusion KLN drug serum can promote myocardial cell spon-taneous extracellular calcium influx,the mechanism of KLN antiarrhythmic effect may be related to the Ca2 + channel.