ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital trap-linear ion-trap mass spectrometry（UPLC-Orbitrap Fusion Lumos Tribrid-MS）， the plasma concentration of ziyuglycoside Ⅰ was determined at different time points after oral administration， and its pharmacokinetic characteristics in normal rats and rats with acute kidney injury were compared. MethodsRats were randomly divided into normal group and model group， the model group received intraperitoneal cisplatin（10 mg·kg^-1） to establish the acute kidney injury model， the normal group was given the same volume of saline. After successful modeling， rats in the normal and model groups were randomly divided into the normal low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1） and the model low， medium and high dose groups（2.5， 5， 7.5 mg·kg^-1）， 6 rats in each group， and the plasma was collected at different time points after receiving the corresponding dose of ziyuglycoside Ⅰ. Then， the concentration of ziyuglycoside Ⅰ in rat plasma was determined by UPLC-Orbitrap Fusion Lumos Tribrid-MS， and the drug-time curve was poltted. The pharmacokinetic parameters were calculated by Kinetica 5.1 software， and the differences in pharmacokinetic parameters between different administration groups were compared by independent sample t-test with SPSS 22.0. ResultsThe pharmacokinetic results showed that after receiving the different doses of ziyuglycoside Ⅰ， its concentration increased first and then decreased， and all of them reached the maximum plasma concentration at about 0.5 h. The area under the curve（AUC_0-t） and mean retention time（MRT_0-t） of normal and model rats increased with the increased dose， and the clearance（CL） decreased with the increasing dose. Compared with the normal group， the AUC_0-t was significantly increased（P<0.01）， peak concentration（C_max） and CL decreased in model rats at different doses， indicating that the physiological state of the rats could affect the absorption and elimination of ziyuglycoside Ⅰ in vivo. ConclusionThe pharmacokinetic characteristics of ziyuglycoside Ⅰ are quite different in normal rats and acute kidney injury model rats， which may be due to the change of the body environment in the pathological state， then lead to changes in absorption and metabolic processes.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Liquid chromatography-electrospray ionization tandem mass spectrometry(LC-ESI-MS)is a widely utilized technique for in vivo pharmaceutical analysis.Ionization interference within electrospray ion source,occurring between drugs and metabolites,can lead to signal variations,potentially compromising quantitative accuracy.Currently,method validation often overlooks this type of signal interference,which may result in systematic errors in quantitative results without matrix-matched calibration.In this study,we conducted an investigation using ten different groups of drugs and their corresponding me-tabolites across three LC-ESI-MS systems to assess the prevalence of signal interference.Such in-terferences can potentially cause or enhance nonlinearity in the calibration curves of drugs and metabolites,thereby altering the relationship between analyte response and concentration for quanti-fication.Finally,we established an evaluation scheme through a step-by-step dilution assay and employed three resolution methods:chromatographic separation,dilution,and stable labeled isotope internal standards correction.The above strategies were integrated into the method establishment process to improve quantitative accuracy.

Objective:To discuss the effects of walking function-guided interactive Tuina(Chinese therapeutic massage)on spatiotemporal gait parameters in children with spastic cerebral palsy(CP). Methods:Fifty children with spastic diplegic CP were divided into an observation group and a control group following a paired design and random number principle,with 25 cases in each group.The observation group was treated with the walking function-guided interactive Tuina,and the control group was offered the"six methods of spine and back"Tuina,20 min for each session and 5 sessions weekly for 3 consecutive months.The children's changes were assessed using the percentage of dimension E(walking,running,and jumping)of the gross motor function measure-88(GMFM-88)and three-dimensional gait analysis. Results:After treatment,the percentage of GMFM-88 dimension of dimension E(walking,running,and jumping)changed significantly in both groups(P<0.05),and the between-group difference was also statistically significant(P<0.05).After treatment,the step length,walking speed,and step frequency changed markedly in the observation group(P<0.05)and were significantly different from those in the control group(P<0.05).After the intervention,the stance phase and double support extended,and the swing phase became shorter in the observation group(P<0.05);the between-group differences were statistically significant(P<0.05).The maximal knee flexion angle and maximal posterior pelvic tilt angle decreased After treatment in the observation group,and the maximal anterior pelvic tilt angle increased,all showing statistical significance(P<0.05);the between-group differences were statistically significant(P<0.05). Conclusion:Compared with the passive Tuina manipulations,the"six methods of the spine and back",walking function-guided interactive Tuina has its advantage in improving walking function in children with spastic CP,manifesting as better lower-limb force line and walking efficiency.

Humans ; Asthma/drug therapy* ; Biological Therapy

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Renal cell carcinoma is a malignant tumor originating from the renal parenchyma. Different subtypes of renal cell carcinoma have different pathological features and molecular mechanisms. Because radiotherapy and chemotherapy are difficult to achieve ideal therapeutic effect on renal cell carcinoma, targeted therapy based on vascular endothelial growth factor and mammalian target of rapamycin will eventually in the case of drug resistance, it is currently necessary to explore a new way to improve the treatment status of metastatic renal cell carcinoma. With the continuous research and exploration of programmed death-1 (PD-1)/programmed death-ligand-1 (PD-L1) inhibitors, immunotherapy certain effects have been shown in metastatic renal cell carcinoma. PD-1/PD-L1 inhibitors have considerable prospects for single-agent or other drug treatment in renal cancer, and the long-term adverse reaction rate of this drug is low. At present, there are studies that treat PD-1 or PD-L1 inhibitors in combination with radiochemotherapy, anti-tumor drugs and surgery, bringing new hope to patients who are not sensitive to radiochemotherapy, are resistant to drugs, and have lost surgery. While PD-1 or PD-L1 also significantly improves overall survival in monotherapy. This article reviews and summarizes the application and research progress of PD-1/PD-L1 inhibitors in renal cell carcinoma in recent years, and reviews them.

Objective To clarify the value of absorbable barbed suture in closure of galeal. Methods A total of 101 patients had craniotomy treated in Shengjing Hospital of China Medical University from October 2018 to February 2019 were divided into two groups according to the admission date. In the barbed suture group, 45 patients were sutured with QUILL by continuous stitching. In the control group, 56 patients were sutured with traditional stitchingby intermittent suture. Compare the differences in suture speed, average postoperative hospital stay, incision complication rate, and the average hospital costs of the two groups. Results The suture speed in barbed suture group was (0.330 ± 0.012) cm/min , and was significantly faster than that in control group (0.540 ± 0.016) cm/min;the postoperative average hospitalization days in barbed suture group was (10.91 ± 0.62) d, and was significantly shorter than that in control group (12.73 ± 0.41) d, there were significant differences (P<0.05) . However, the complications and hospital costs in two groups had no significant differences (P>0.05). Conclusions The use of absorbable barbed close epicranial aponeuroisiscan improve suture speed, shorten the postoperative average hospitalization days, which is worthy of promotion.

Objective To explore the changes of whole brain white matter ( WM) structural net-work topological property in patients with schizophrenia (SP) and the associations between WM networks to-pological efficiency and clinical variables in patients. Methods Deterministic tractography was used to con-struct the WM networks of 59 patients with SP ( patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs),and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients. Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in pa-tients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM net-works. However,compared with HCs,the patients with SP exhibited significant abnormal global topology,in-cluding increased shortest path length ( t=7. 95, P=0. 0001) and decreased global efficiency ( 30. 83 ± 16. 08,8. 25±6. 13,t=-9. 81,P=0. 002),clustering coefficiency (0. 03±0. 01,0. 02±0. 01,t=-4. 48,P=0. 0003),the average clustering coefficiency (t=-8. 28,P=0. 002),the small-worldness (3. 92±0. 79,2. 79 ±0. 56,t=-7. 82,P=0. 001) of their WM structural networks(all P<0. 005,FDR corrected). Further,the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus ( t=-4. 11, P=0. 000),superior occipital gyrus ( t=-6. 05, P=0. 002), superior temporal gyrus ( t=-10. 46, P=0. 001),middle temporal gyrus (t=-10. 38,P=0. 000),thalamus (t=-6. 10,P=0. 000) and putamen ( t=-8. 38,P=0. 000) (P<0. 005,FDR corrected). Partial correlation results showed that there was no signifi-cant correlation between global topological properties,node efficiency and clinical symptoms in patients group (Eglob:r=-0. 14,P=0. 279;Eloc:r=-0. 06,P=0. 628;Lp:r=0. 28,P=0. 031;Cp:r=0. 27,P=0. 043;λ:r=-0. 18,P=0. 166;γ:r=-0. 29,P=0. 026;σ:r=0. 26,P=0. 048;nEglob:r=0. 36,P=0. 005;nEloc:r=0. 02,P=0. 901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly re-duced.

Objective To explore the relationship between MTHFR gene polymorphism and lung cancer in Han population of Heilongjiang Province.Methods Two hundred and twenty-five lung cancer patients were selected as the experimental group and the healthy subjects in the outpatient physical examination as the control group,A case-control study was used to analyze the association of MTHFR gene 677C/T,1298A/C SNP and lung cancer,and the gene typing was detected by Sanger double deoxidization chain termination method.Results In the control group,the frequencies of wild-type CC,mutant heterozygote CT,and homozygous TT genotypes of the MTHFR gene C677T were 34.2％,55.1％,and 10.7％,respectively.The frequencies of the three genotypes in the experimental group were 26.7％,50.2％,23.1％,respectively.The difference in the distribution of C677T SNP genotype frequencies of the experimental group and the control group was statistically significant (P =0.002),in which the mutation homozygous TT carriers were 2.78 times more likely to develop lung cancer than wild-type CC (OR(95％CI):2.78 (1.54 ～ 5.02),P =0.001);AA,AC and CC genotype frequencies ofthe A1298C locus of the MTHFR gene were 34.2％,55.1％,and 10.7％,respectively,and the control group was 64.0％.32.0％,4.0％,there was no significant difference between the two groups (P =0.247).The frequencies of AA,AC and CC genotypes in the A1298C locus of the MTHFR gene were 34.2％,55.1％,and 10.7％,respectively,and 64.0.％,32.0％,and 4.0％ in the control group,respectively.There was no significant difference between the two groups (P).=0.247).The haploid analysis showed that the distribution frequency of TA haplotype in the experimental group was significantly higher than that in the control group (43.1％ vs.35.3％).There was a statistically significant difference between the two groups (OR(95％CI):1.39 (1.06-1.81),P=0.016);while the frequencies of CC haplotypes in the experimental group and the control group were 10.6％ and 17.1％,respectively.The difference was statistically significant (OR(95％CI):0.58 (0.39-0.85).P=0.005).There was a linkage disequilibrium between the two points of MTHFR gene 677 and 1298 (D'=0.48,P=0.003).The gene-environment interaction analysis of the MTHFR gene C677T polymorphism showed that based on the comparison between TT and CC genotype,age over 60 (OR(95％CI):4.0(1.78-9.32),P =0.001),male (OR (95％CI):5.55 (2.10-14.67),P=0.000),smoking (OR(95％CI):8.13 (2.29-28.85),P=0.000) and small cell lung cancer (OR (95％CI):1.28 (1.10-1.44),P=0.000) can increase the risk of lung cancer;based on the comparison between CT and CC genotype,women (OR(95％CI):2.09 (1.05-4.16),P=0.030),non-smoking population (OR(95％CI):2.43 (1.25-4.74),P=0.008) and small cell lung cancer (OR (95％ CI):0.31 (1.16-1.59),P =0.000) can increase the risk of lung cancer.Conclusion MTHFR gene C677T is a genetic susceptibility gene for lung cancer and is associated with the risk of lung cancer.