ObjectiveTo investigate whether Danggui Shaoyaosan （DSS） inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 1 （ROCK）/nuclear factor kappa-B （NF-κB） signaling pathway， thereby delaying the progression of diabetic kidney disease （DKD） and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group， and forty 8-week-old db/db mice were randomly divided into the model group， DSS low-dose group （8.39 g·kg^-1）， DSS medium-dose group （16.77 g·kg^-1）， DSS high-dose group （33.54 g·kg^-1）， and irbesartan group （0.025 g·kg^-1）， with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration， changes in body weight， fasting blood glucose （FBG）， and 24 hour urinary protein （24 h UTP） were observed. After 12 consecutive weeks of administration， hematoxylin-eosin （HE） staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species （ROS） in renal tissue were detected using the dihydroethidium （DHE） method. The expression levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in renal tissue were determined. Serum interleukin-1β （IL-1β） and interleukin-6 （IL-6） levels were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of RhoA， ROCK1， and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. Protein expression levels of fibronectin （FN）， Collagen Ⅳ（Col Ⅳ）， transforming growth factor-β₁ （TGF-β₁）， RhoA， ROCK， and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group， the model group showed significantly increased body weight， FBG， and 24 h UTP levels （P<0.01）， elevated serum IL-1β and IL-6 levels， enlarged glomerular volume， diffuse mesangial expansion， increased mesangial matrix， and marked collagen fiber proliferation in renal tissues. SOD activity was decreased， while MDA， ROS， RhoA， ROCK1， and NF-κB p65 mRNA expression levels were increased （P<0.01）， and the protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 were also elevated （P<0.01）. Compared with the model group， the DSS low-， medium-， and high-dose groups and the irbesartan group showed reductions in body weight， FBG， and 24 h UTP， decreased serum IL-1β and IL-6 levels， varying degrees of improvement in renal histopathology， increased SOD activity， decreased MDA levels， reduced ROS expression， and significantly downregulated RhoA， ROCK1， and NF-κB p65 mRNA expression （P<0.05， P<0.01）， as well as reduced protein expression levels of FN， Col Ⅳ， TGF-β₁， RhoA， ROCK， and NF-κB p65 （P<0.05， P<0.01）. ConclusionDSS can alleviate oxidative stress and inflammation， reduce extracellular matrix deposition， and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway， thereby exerting a therapeutic effect on DKD.

OBJECTIVE: To explore the corrective strategies and effectiveness of osteotomy surgery for severe lower limb deformities in hypophosphatemic rickets. METHODS: A retrospective analysis was conducted on 29 patients with severe lower limb deformities of hypophosphatemic rickets who underwent surgical treatment between February 2012 and August 2024. There were 9 males and 20 females. The age ranged from 13 to 53 years, with an average of 24.6 years. All patients were deformities of both lower limbs, presenting as 24 cases of O-shaped legs, 2 cases of wind-blown deformities, and 3 cases of X-shaped legs. Based on the full-length films of both lower limbs in the standing position before operation, the osteotomy planes of the femur, tibia, and fibula were designed. Among them, if both the same-sided thigh and leg were deformed, staged surgeries of both lower limbs were selected. If only the thigh or leg were deformed, simultaneous surgeries of both lower limbs were selected. The femur deformity was corrected immediately after osteotomy at the deformed plane; the osteotomy fragment was temporarily controlled with an external fixator, which was removed after perform internal fixation with a steel plate. After fibular osteotomy, the Ilizarov frame or Taylor frame was installed on the tibia and fibula. The threaded rods were removed and then tibial osteotomy was performed on the deformed plane. Patients using the Taylor frame did not undergo deformity correction during operation. The external fixators were adjusted starting 7 days after operation to correct the varus, valgus, and rotational deformities of the lower limb. Patients using the Ilizarov frame corrected the rotational deformity of the tibia during operation. The external fixator was adjusted starting 7 days after operation to correct the varus and valgus deformities of the lower limb. During the treatment period, the patient could walk with partial weight-bearing on the operated limb with crutches. The external fixator was removed after the bone healed. Before operation and at last follow-up, the medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), posterior proximal tibial angle (PPTA), anterior distal tibial angle (ADTA), anatomic lateral distal femoral angle (aLDFA), posterior distal femoral angle (PDFA), and mechanical axis deviation (MAD), lower limb rotation, limb length discrepancy (LLD) were measured. The self-made scoring criteria were adopted to evaluate the degree of lower limb deformity of the patients. RESULTS: All operations were successfully completed, and no complications such as nerve or vascular injury occurred. The adjustment time of the external fixator of the lower limb after operation was 28-46 days, with an average of 37.4 days. The wearing time of the external fixator ranged from 134 to 398 days, with an average of 181.5 days. Mild pin tract infections occurred in 2 limbs. The osteofascial compartment syndrome occurred in 1 limb after operation. No complications related to orthopedic adjustment of the external fixator occurred in other patients. All patients were followed up 6-56 months, with an average of 28.2 months. At last follow-up, full-length films of both lower limbs in the standing position showed that the coronal mechanical axes of the lower limbs of all patients returned to the normal. At last follow-up, MPTA, LDTA, PPTA, aLDFA, PDFA, MAD, lower limb rotation, LLD, and the score of lower limb deformity significantly improved when compared with those before operation ( P<0.05). There was no significant difference in ADTA between pre- and post-operation ( P>0.05). The degree of lower limb deformity were rated as moderate in 2 cases and poor in 27 cases before operation and as excellent in 7 cases, good in 18 cases, and moderate in 4 cases at last follow-up, with an excellent and good rate of 86.2%. CONCLUSION For severe lower limb deformities in hypophosphatemic rickets, immediate correction of deformities with femoral osteotomy and internal plate fixation, as well as gradually correction of deformities with tibiofibular osteotomy and circular external fixation (Ilizarov frame or Taylor frame), have satisfactory therapeutic effects.
Humans ; Male ; Osteotomy/instrumentation* ; Female ; Adult ; Retrospective Studies ; Tibia/abnormalities* ; Adolescent ; Femur/abnormalities* ; Middle Aged ; Fibula/surgery* ; Rickets, Hypophosphatemic/complications* ; Young Adult ; Treatment Outcome ; External Fixators ; Bone Plates ; Lower Extremity Deformities, Congenital/etiology*

OBJECTIVE To investigate the causal association between ticagrelor and risk of infection METHODS Two-sample Mendelian randomization was adopted. Genetic instrumental variables were selected based on the results of the largest genome-wide association analysis to in vivo exposure of ticagrelor and its major active metabolite AR-C124910XX. The causal associations of ticagrelor and its major active metabolite AR-C124910XX with drug indications （coronary artery disease， unstable angina pectoris， myocardial infarction， stroke and ischemic stroke）were analyzed by inverse variance weighted Mendelian randomization model as a positive control for genetic instrumental variables. The causal relationship between ticagrelor and bacterial infection， acute lower respiratory infection， bacterial pneumoniae， pneumoniae，acute upper respiratory infection and sepsis were furtheranalyzed by using this method， and the robustness of the results was assessed by using heterogeneity tests and horizontal 202002030415） pleiotropy tests. RESULTS The increase of area under the curve at steady state （AUCss） of the genetic surrogated ticagrelor significantly reduced the risk of coronary artery disease， myocardial infarction and unstable angina pectoris （P＜0.001）. AUCss genetic instrument variables of its main active metabolite AR-C124910XX failed to pass positive control. Further analysis showed that the increase of the genetic surrogated ticagrelor exposure suggestively reduced the risk of bacterial infection [OR（95%CI）＝0.80（0.65，0.99），P＝0.040] and sepsis [OR （95%CI）＝0.84（0.73， 0.98）， P＝0.023]. The results of the heterogeneity tests showed that there was no heterogeneity in the causal association of the genetic surrogated ticagrelor AUCss with bacterial infection and sepsis （P＞0.05）. The results of horizontal pleiotropy tests showed that the causal association of genetic surrogated ticagrelor AUCss with bacterial infection and sepsis had no effects on horizontal pleiotropy （P＞0.05）. CONCLUSIONS Ticagrelor has a potential role in reducing the risk of sepsis and bacterial infections.

Objective To explore the changes of serum amyloid A (SAA) level and its clinical significance in patients with post-stroke depression (PSD). Methods One hundred and sixty-four patients with acute ischemic stroke, admitted to our hospital from January 2016 to June 2017 were assessed with Hamilton Depression Scale-17 (HAMD-17) to evaluate the depression degrees, and accordingly, they were divided into PSD group (n=57) and non-PSD group (n=107). Healthy volunteers who were examined in the corresponding period were selected as healthy control group (n=50). The SAA level was determined with ELISA in subjects of the 3 groups. Clinical data were collected; single factor analysis and multivariate Logistic regression analysis were performed to select the risk factors of PSD. Results The SAA level in PSD group ([18.85±5.25] mg/L) was significantly higher than that in the non-PSD group ([15.25±5.75] mg/L) and healthy control group ([7.65±4.50] mg/L, P<0.05); that in the non-PSD group was significantly higher than that in the healthy control group (P<0.05). Single factor analysis showed that differences in education level, introversion, economic status, living alone, marital status, National Institutes of Health Stroke Scale (NIHSS) scores≥9 at admission, complications, and proportion of key area infarction (frontal lobe and basal ganglia) had statistical significance between PSD group and non-PSD group (P<0.05). Multivariate Logistic regression analysis showed that introversion, poor economic status, living alone, NIHSS scores≥9, infarction of key areas, and elevation of SAA level (OR=1.545, P=0.035, 95％ CI: 1.257-1.898) were independent risk factors for PSD (P<0.05). Conclusion SAA used as one of the detection biomarkers has great significance in early diagnosis, intervention and clinical prevention for PSD.

Objective To discuss the feasibility and reproducibility of left ventricular volume and function of patients with left atrial remodeling and left ventricular remodeling by 3-dimensional echocardiography HeartModel (3D-HM).Methods Three-dimensional images of 156 subjects were collected under HMACQ imaging mode.They were assigned into three groups:① control group (group A,n =70);② group of left ventricular remodeling after,acute myocardial infarction (group B,n =17);③group of hypertension left atrial remodeling (group C,n =69).3D-HM method was used for quantifying left ventricular end-diastolic volume (LVEDV),left ventricular end-systolic volume (LVESV),left atrial end-systolic volume (LAESV) and left ventricular ejection fraction (LVEF),and the results were compared with conventional 3D-manual results.The reproducibility of the 3D-HM method within one group and among different groups was evaluated.Results There was a significant difference in all the parameters measured with the 3D-HM method in different groups(P ＜0.05).LVEDV,LVESV,and LAESV in group B were higher than those in group A and group C(P ＜0.05),and LVEF was lower than that in group A and group C(P ＜0.05),LAESV of group C was higher than that of group A(P ＜0.05).The difference in the measurements of LVEDV and LVESV between the two methods was greatest in group B compared with group C and group A(P ＜0.05).In group C,the measured value difference of LAESV between two methods was greater than that of group A (P =0.03).There was closer correlation among LVEDV,LVESV,LAESV and LVEF measured values of 3D-HM method as well as measured values of the 3D-manual method (r =0.94,0.97,0.91 and 0.90).The data post-processing time of 3D-HM was significantly shorter than that of 3D-manual (P ＜0.05).The inter-observer and intra-observer difference of measured values of 3D-HM method had no statistical significance (P ＞0.05).Conclusions 3D-HM is a fast and feasible technique with high reproducibility for quantifying the left ventricular volume and function in patients with left atrial remodeling and left ventricular remodeling.

Objective To investigate the effects of sodium butyrate on ethanol-seeking behavior and H3K9 acetylation levels in NMDA receptor 2B subunit(NR2B) promoter region in the hippocampus of Wistar rats.To explore the epigenetic mechanism underlying ethanol-seeking behavior.Methods According to random number table,48 male Wistar rats were divided into saline group,sodium butyrate group,ethanol group and sodium butyrate + ethanol group,with 12 rats in each group and administered by intraperitioneal injection respectively.Conditioned place preference (CPP)was used to evaluate the ethanol-seeking behavior.Using Western-blot,real-time PCR and chromatin immunoprecipitation assays,the expression of NR2B protein,NR2BmRNA and the relative level acetylated H3K9 in NR2B promoter region in the hippocampus were determined respectively.Results The CPP test and the CPP score in each group were different (P＜ 0.05).Compared with the CPP test(261.1 ± 102.2) and the CPP score(48.5±94.6) of saline group,the CPP test ((406.8±109.2),(502.7±72.89)) and the CPP score((198.2± 119.4),(277.5±76.2)) of ethanol group and sodium butyrate + ethanol group were significantly higher(P＜0.05),the CPP test(193.4±93.8) and the CPP score (9.7±94.0)of sodium butyrate group were not significantly different(P＞0.05).Compared with the ethanol group,CPP test of sodium butyrate + ethanol group was significantly higher(P＜0.05).The expression of NR2B protein,NR2BmRNA and acetylated level H3K9 in NR2B promoter region in the hippocampus in each group were different (P＜ 0.05).Compared with the expression of NR2B protein (1.00 ± 0.28),NR2BmRNA(1.00±0.14) and H3K9 acetylation in NR2B promoter region(1.00±0.25)in the hippocampus of saline group the expression of NR2B protein((1.40±0.34),(1.79±0.30)),NR2BmRNA((1.26±0.16),(1.50±0.08)) and aeetylated level H3K9 in NR2B promoter region ((1.68±0.16),(2.35±0.45)) of ethanol group and sodium butyrate ± ethanol group were significantly higher(P＜0.05).The expression of NR2B protein(0.85±0.24),NR2BmRNA(1.05±0.13) and acetylated level H3K9 in NR2B promoter region(0.96±0.41) of sodium butyrate group were not significantly different(P＞0.05).Compared with the ethanol group,the expression of NR2B protein,NR2BmRNA and acetylated level H3K9 in NR2B promoter region in the hippocampus of ethanol group,these of sodium butyrate + ethanol group were significantly higher (P＜0.05).The CPP score were positively correlated with the expression of NR2B protein (r=0.474,P＜0.05).The expression of NR2B protein were positively correlated with the expression of NR2BmRNA (r=0.468,P＜0.05).The expression of NR2BmRNA were positively correlated with the expression of H3K9 acetylation in NR2B promoter region(r=0.596,P＜0.05),and the CPP score were positively correlated with the expression of H3K9 acetylation in NR2B promoter region (r=0.542,P＜0.05).Conclusion The increasing acetylation level of H3K9 in NR2B promoter region in the hippocampus may be one of the epigenetic mechanisms of promoting ethanolseeking behavior,and H3K9 deacetylation in NR2B promoter region in the hippocampus is likely to be a new target for controlling ethanol dependence.

OBJECTIVE:To provide reference for standardizing the names of TCM from Rumex. METHODS:According to lit-erature research,the most frequently used names (such as Jinbuhuan,Tudahuang,Yangti) of TCM in Rumex were combed,and suggestions for existing problems were put forward. RESULTS & CONCLUSIONS:The TCM names were used confusedly,main-ly showing that inconsistent names of TCM from the same plant in different areas,same name of TCM from different plants in the same area,same name of TCM from different plants in different areas. The key to solving the confused use of names of TCM in Rumex is standardization and unification of medicinal plant source and names. It can be developed and solved in order by resource investigation and identification,establishing quality standard and excavating medicinal value,in which,conducting the resource in-vestigation and specie identification,determining the medicinal names,stipulating the official names and establishing the quality standard are the important work in future.

Objective To evaluate the changes ofcerebrovascular reserve (CVR) of patients with obstructive sleep apnea hypopnea syndrome (OSAHS) by transcranial cerebral doppler (TCD) and to study its relation with stroke.Methods One hundred and twenty-six patients with OSAHS,admitted to our hospitals from July 2012 to January 2013 and diagnosed as having OSAHS,were chosen in our study;they were divided into mild OSAHS group (n=49),moderate OSAHS group (n=44) and severe OSAHS group (n=33) according to test results of polysomnography (PSG).Another 40 healthy controls were collected.The CVR of all subjects were evaluated by TCD merging with CO2 experiment and compared among different groups.All the subjects were accepted continued two-year follow-up and recorded the accidents of stroke.The morbidities of stroke were compared between different groups.Results As compared with those in the control group and mild OSAHS group,all of the contractile reserve,dilatation reserve and overall reserve descended in moderate OSAHS group and severe OSAHS group with statistically significant differences (P＜0.05).As compared with those in the moderate OSAHS group,all of the contractile reserve,dilatation reserve and overall reserve descended in severe OSAHS group,and the differences were statistically significant (P＜0.05).In the two years of follow-up,the incidence of stroke in the severe OSAHS group (12.12％) was significantly higher than that in the control group (0％),mild OSAHS group (0％) and moderate OSAHS group (4.55％,P＜0.05).Conclusion The heavier the condition of OSAHS,the more obviously descended the CVR;the stroke morbidity of severe OSAHS patients is increased significantly.

Objective: To explore the effect of salinomycin on the metastasis and invasion of bladder cancer cell line T24 by regulating the related protein expression in the process of epithelial-mesenchymal transition (EMT), and to provide experimental basis for the treatment of urological tumors. Methods: The bladder cancer cell line T24 was cultured in vitro. The rat bladder tumor model was established in vivo. The rats were randomized into two groups, among which the rats in the experiment group were given intraperitoneal injection of salinomycin, while the rats in the control group were given intraperitoneal injection of normal saline. The change of tumor cells in the two groups was observed. Transwell was used to detect the cell migration and invasion abilities, Real-time PCR was used to detect the expression of mRNA, while Western-blot was utilized for the determination of the expressions of E-cadherin and vimentin proteins. Results: The metastasis and invasion abilities of serum bladder cancer cell line T24 after salinomycin treatment in the experiment group were significantly reduced when compared with those in the control group, and the tumor metastasis lesions were decreased from an average of 1.59 to 0.6 (P < 0.05). T24 cell proliferation in the experiment group was gradually decreasing. T24 cell proliferation at 48 h was significantly lower than that at 12 h and 24 h (P < 0.05). T24 cell proliferation at 24 h was significantly lower than that at 12 h (P < 0.05). T24 cell proliferation at each timing point in the experiment group was significantly lower than that in the control group (P < 0.05). The serum mRNA level and E-cadherin expression in the tumor tissues in the experiment group were significantly higher than those in the control group, while vimentin expression level was significantly lower than that in the control group (P < 0.05). Conclusions: Salinomycin can suppress the metastasis and invasion of bladder cancer cells, of which the mechanism is probably associated with the inhibition of EMT of tumor cells.

Objective To observe the effects of different concentrations of glucose on the proliferation and differentiation of primary osteoblasts.Methods The identification of mouse primary osteoblasts was performed by alkaline phosphatase (ALP)staining and Von Kossa staining.Treating osteoblasts with different dose of glucose (5.5,15.5,25.5 mmol/L),the osteoblasts proliferation,ALP staining,and Runx2,OB markers ALP and OCN mRNA expression were observed.Real-time PCR was used for the determination of Runx2,OB markers ALP and OCN mRNA expression.Results With the increasing glucose concentrations,the osteoblasts cell proliferation was decreased.Compared with 5.5 mmol/L normal glucose,the ALP staining in 15.5 mmol/L group and 25.5 mmol/L group were decreased.The expressions were decreased by (36.7±6.2)％ and (38.3±2.2)％ in Runx2 mRNA,(26.7±7.2)％ and (40.4±4.3)％ in OCN mRNA respectively.ALP in 15.5 mmol/L group was reduced by (33.3±10.2)％,but increased by(50.8±10.4) ％ in 15.5 mmol/L group.Conclusions High glucose may decrease osteoblasts proliferation and activity,which may be one of the key pathogenesis factors of diabetic osteoporosis.