Objective: To investigate the inhibitory effects and induction of apoptosis on human gastric adenocarcinoma cells (SGC 7901) by genistein. Methods: MTT、 colony forming experiment、 electon microscope and FCM were used to study the effects of genistein on SGC 7901.Results: MTT and colony forming experiment showed that the genistein inhibited SGC 7901 growth. Electron microscope and FCM showed that genistein could induce apoptosis. [WT5HZ]Conclusion: [WT5BZ]Genistein inhibits SGC 7901 cells growth via apoptosis induction.

Objective To explore the mechanism of rapamycin-eluted stent in vascular endothelial injury. Meth?ods (1)Rapamycin (rapamycin group) was injected to rabbit dorsum muscle to simulate rapamycin-eluted stent implanta?tion into muscles. Control group and acetone control group were established at the same time. Morphological change in mus?cle was observed and serum calcium levels were measured after rapamycin injection.(2)HUVECs were incubated with 0.1, 1, 10 and 100μg/L rapamycin for 48 h respectively or with 1μg/L rapamycin for 6, 12, 24 and 48 h respectively.Cell via?bility was examined by MTT and its relationship with drug concentration and treatment time were analyzed.(3)HUVECs were divided into control group and 1μg/L rapamycin group. After 48 h,morphological changes of HUVECs were assessed by HE staining,the production of nitric oxide was examined by Nitric Oxide Assay Kit and the intracellular calcium ion con?centration was tagged with Fluo-3/AM. Results (1) Organizational morphology in local muscle with rapamycin injection represent stent implantation of rabbit,and calcium content in local muscle increased significantly in rapamycin group com?pared with nomal control group and acetone control group(P<0.05). (2) Cell survival rate decreased significantly upon ad?ministration of rapamycin in both concentration and time dependent manner(P<0.01). (3) In rapamycin group, cytoplasm vacuoles, nucleus pycnosis and nuclear fragmentation were observed;compared with control group,the levels of intracellular free Ca2+increased while the levels of nitric oxide was reduced. Conclusion Rapamycin treatment lead of injury to vascular endothelial cells which might through up-regulating intracellular Ca2+level.

Objective To investigate the effects of ulinastatin (UTI) combined with magnesium isoglycyrrhizinate (MgIG) on the expression of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) in lung tis?sue of rats with pulmonary fibrosis induced by bleomycin (BLM). Methods Ninety Wistar rats were randomly divided into five groups: BLM group, methylprednisolone (MTH) group, UTI group, MgIG group and UTI combined with MgIG (UTI+MgIG) group, n=18 for each group. The rat model of pulmonary fibrosis was established by injecting bleomycin through tra?chea in five groups. Twenty-four hours after treatment with BLM,rats were treated with normal saline every day in BLM group, and rats were treated by corresponding drugs in other groups. Six rats of each group were killed at the 7th,14th and 28th day respectively. The pathological changes of alveolitis and pulmonary fibrosis were evaluated by HE staining, and ex?pression levels of TGF-β1 and CTGF in lung tissues were detected by immunohistochemistry method. Results (1) Com?pared with BLM group, the degree of alveolitis and pulmonary fibrosis was reduced in other groups. There was significant dif?ference in alveolitis at the 7th and 14th day between UTI+MgIG group and BLM group. And there was significant difference in pulmonary fibrosis at the 14th and 28th day between UTI+MgIG group and BLM group (P<0.05). (2) Compared with BLM group, the expression levels of TGF-β1 and CTGF were decreased in other groups. In UTI+MgIG group, the expres?sion levels of TGF-β1 were significantly lower at the 7th and 14th day compared with those in UTI group and MgIG group, and which were significantly lower at the 28th day than those in MTH group, UTI group and MgIG group (P<0.05). The ex?pression levels of CTGF were significantly lower at the 7th day in UTI + MgIG group than those in UTI group and MgIG group, and which were significantly lower at the 14th and 28th day than those in MTH group, UTI group and MgIG group (P<0.05). Conclusion The combination of UTI and MgIG can alleviate alveolitis and fibrosis in BLM-induced pulmonary fibrosis rats, which might related with the down-regulation of TGF-β1 and CTGF expressions.

OBJECTIVE:To investigate the effects of blood concentration monitoring of cylosporin A(CsA) in patients with nephrotic syndrome(NS)on efficacy and safety. METHODS:The medical records of 154 NS patients receiving CsA and blood concentration monitoring in nephrology department of China-Japan Friendship Hospital during Jan. 2014-Aug. 2017 were analyzed retrospectively. The results of blood concentration monitoring in 63 adult inpatients with refractory NS receiving CsA for the first time within 6 months of initial treatment were analyzed statistically. The relationship of blood concentration monitoring with efficacy and safety was analyzed. RESULTS:The blood concentration of CsA in 154 patients were monitored for 512 times with an average of 3.32 times/person,and average blood concentration was(125.98±105.13)ng/mL. The patients with blood concentration of CsA＜100 ng/mL accounted for 44.14%. There was no statistical significance in average monitoring times or average blood concentration between male and female,average blood concentration of CsA among different age groups (P＞0.05). The blood concentration was monitored for 237 times in 63 adult inpatients with refractory NS receiving CsA for the first time within 6 months of initial treatment(induction period). Average blood concentration of effective group were significantly higher than ineffective group;the proportion of effective group with blood concentration＜100 ng/mL was significantly lower than that of ineffective group,with statistical significance (P＜0.05). Among 63 patients,17 patients suffered from ADR (the incidence of ADR was 26.98%). The average blood concentrations of ADR patients were significantly higher than those without ADR;the monitoring times of ADR patients with blood concentration＞150 ng/mL was significantly higher than those without ADR,with statistical significance(P＜0.05). There was no statistical significance in the incidence of ADR between effective group and ineffective group (P＞0.05). Among effective group,there was no statistically significance in average blood concentration between ADR patients and patients without ADR(P＞0.05);the monitoring times of ADR patients with blood concentration＞150 ng/mL was significantly higher than patients without ADR,with statistical significance(P＜0.05). With the increase of monitoring times,the incidence of ADR decreased gradually. There was no statistical significance in the incidence of ADR among patients who were monitored for different times (P＞0.05). CONCLUSIONS:The pharmacokinetics of CsA varies in different patients and many factors affect its blood concentration. The changes of blood concentration affect the efficacy and safety of CsA. It is difficult to determine the dosage of CsA based on experience in the treatment of NS with CsA. Great importance should be attached to blood concentration monitoring of CsA and the implementation of individualized dosage regimen based monitoring results so as to improve therapeutic efficacy and reduce the occurrence of ADR.

Objective:To evaluate the effects of peroneal osteotomy combined with arthroscopic knee debridement on perioperative indexes, X-ray indexes, Japanese Orthopaedic Association Assessment score (JOA score), American Hospital for Special Surgery knee score (HSS score) and complication rate of patients with knee osteoarthritis.Methods:A prospective research method was adopted. A total of 110 patients with knee osteoarthritis who were admitted to Chengde Central Hospital from April 2016 to April 2021 were selected as the research objects and divided into the control group (55 cases), the combined group (55 cases) by random number table method. The control group underwent arthroscopic debridement of the knee joint. On the basis of the control group, the combined group was combined with fibula osteotomy. The control group and the combined group were followed up for 6 months after operation. The perioperative indicators, score of JOA before and after 1 month of treatment, X-ray indicators, score of HSS before and after 6 months of treatment, and the incidence of complications during the follow-up period were compared between the control group and the combined group.Results:The operation time of the combined group was longer than that of the control group: (84.36 ± 14.64) min vs. (75.88 ± 12.86) min; compared with before operation, 1 month after operation, the scores of swelling, pain while up and down stairs, walking pain, joint range of motion were increased in the control group and the combined group, and the combined group was higher than the control group: (8.35 ± 0.73) points vs. (6.74 ± 0.67) points, (15.05 ± 1.74) points vs. (13.96±1.66) points, (21.75 ± 2.07) points vs. (18.58 ± 1.73) points, (27.59 ± 3.25) points vs. (25.74 ± 2.83) points; the femoral tibial angle and the range of motion of the knee joint in the control group and the combined group were increased, and the combined group was greater than the control group: (1.94 ± 0.60)° vs. (3.02 ± 0.67)°; the scores of stability, flexion deformity, muscle strength, range of motion, function, and pain in the control group and the combined group increased, and the combined group was higher than the control group: (8.62 ± 0.86) points vs. (6.89 ± 0.78) points, (7.86 ± 0.96) points vs. (6.27 ± 0.68) points, (7.79 ± 0.62) points vs. (6.95 ± 0.57) points, (14.95 ± 2.60) points vs. (12.48 ± 2.33) points, (17.46 ± 2.21) points vs. (14.59 ± 1.76) points, (24.83 ± 3.25) points vs. (18.59 ± 2.57) points, the difference was statistically significant ( P<0.05). During the following up period, there were no significant differences in the incidences of osteofascial compartment syndrome, neurovascular injury, intraarticular adhesion and incision infection between the two groups ( P>0.05). Conclusions:The operation time of fibular osteotomy combined with arthroscopic debridement of knee joint in patients with knee osteoarthritis was longer, but fibular osteotomy combined with arthroscopic debridement of the knee joint can reduce the valgus of the patient and improve the range of motion of the joint. It could effectively reduce the degree of pain and improve the function of knee joint, and the safety was good, with good therapeutic effect.

Objective To observe the host response and the expression of interleukin-4 (IL-4) in different cross-linked hyaluronic acid composite gels at different time points after the implantation in vivo, and to explore the significance of biocompatibility and macrophage polarization in post-implantation inflammatory response and tissue remodeling. Methods New Zealand white rabbits were respectively injected with crosslinked hyaluronic acid-crosslinked hydroxypropyl methylcellulose gel (sample 1), crosslinked hyaluronic acid-hydroxypropyl methylcellulose gel (sample 2) and commercially available modified sodium hyaluronate gel (control) in subcutaneous tissue at both sides of the spine. Then the rabbits were dissected at 1, 4 and 12 weeks after the implantation. The tissues were fixed with 10％formaldehyde solution, embedded in paraffin and sliced. Hematoxylin-eosin (HE) staining was performed to observe the degree of inflammation and fibrosis. Masson staining was performed to observe the formation of collagen fibers. Immunohistochemical staining was performed to observe the expression of IL-4. Results The results of HE staining showed that the inflammatory reaction in the sample 1 and sample 2 groups was significantly higher than that in the control group 1 and 4 weeks after the implantation. The inflammatory cells aggregated, and the wall of capsule and microcapsule was thick. The sample 1 group was more obvious, and the result was mild stimulation. For all the groups, the results were all non-irritating at 12 weeks after the implantation. The results of Masson staining showed that the collagen fibers in the sample 1 and sample 2 groups were increased compared with the control group, mainly distributed around the implantation site, and a small amount among the gels after 1 and 4 weeks. After 12 weeks, the collagen fibers were further increased, especially among the gels, which were consistent with the control group. The results of immunohistochemical staining showed that, at the same time point, the expression of IL-4 in sample 1 and sample 2 groups was higher than that in the control group, and the expression of IL-4 increased gradually with time. The expression of IL-4 in the control and sample 1 group at 12 weeks after the implantation was higher than that at 1 and 4 weeks respectively, and the differences were statistically significant (all P<0.05). In the sample 1 group, the expression of IL-4 at 12 weeks after the implantation was higher than that at 1 week, and the difference was statistically significant (P<0.05). The expression of IL-4 in the sample 1 group was significantly higher than that in the control group at 4 weeks after the implantation, and the difference was statistically significant (P<0.05). Conclusions The two different cross-linked sodium hyaluronate composite gels have good biocompatibility. The formation of collagen fiber and the expression of IL-4 can gradually increased within 12 weeks after the subcutaneous implantation, which is beneficial to the tissue remodeling.

Objective:To explore the application value of non-invasive prenatal testing (NIPT) technology in twin pregnancy.Methods:A total of 339 twin pregnant women who underwent NIPT at Dalian Municipal Women and Children′s Medical Center(Group), Dalian Jinpu New District Maternity and Child Health Hospital, and Dalian Lvshunkou District People′s Hospital from July 1, 2019 to June 30, 2021 were continuously retrospectively included. The clinical characteristics and test results of pregnant women with high-risk and low-risk were analyzed.Results:Among 339 pregnant women, 336 were successfully tested, with a success rate of 99.12%(336/339); 6 pregnant women were at high risk of NIPT, with a positive screening rate of 1.77%(6/339), including 1 case of high risk of trisomy 13, 2 cases of high risk of trisomy 18, and 3 cases of high risk of Trisomy 21; the results of amniocentesis for 2 high-risk pregnant women were not abnormal.Conclusions:NIPT technology is non-invasive, safe and efficient, and is suitable for large-scale prenatal screening. However, the detection accuracy of pregnant women with twin pregnancy needs to be improved.

Objective:To establish an ultrasound radiomics model by integrating clinical, pathological, and conventional ultrasound features with radiomics characteristics, and to explore its clinical value in predicting endocrine resistance in hormone receptor(HR)-positive breast cancer.Methods:A retrospective analysis was performed on 478 patients with HR-positive breast cancer from January 2017 to December 2021 in the Second Affiliated Hospital of Harbin Medical University, of which 430 were resistant and 48 were sensitive. The clinical, pathological and immunohistochemical data and ultrasound images were collected.Firstly, the propensity score was used to process and match the data. Secondly, Logistic regression was used to screen clinical, pathological, and conventional ultrasound features associated with endocrine resistance. Then, PyRadiomics was used to extract the radiomic features of grayscale ultrasound images, and a series of methods such as Lasso regression were used to screen the radiomic features related to endocrine resistance. Seven machine learning methods such as random forest were used to build a radiomics model. Finally, clinical, pathological and ultrasound features were added to establish a clinical pathological model, a clinical pathological ultrasound model, a clinical pathological radiomics model and a combined model of the four features, and the model effectiveness was evaluated.Results:①Propensity score matching: 96 patients were matched, including 48 patients in the drug-resistant group and 48 patients in the sensitive group. ②Screening clinical pathological conventional ultrasound features related to endocrine resistance: lymph node metastasis, tumor diameter, posterior echo attenuation, and growth orientation were independent predictors of endocrine resistance (all P<0.05). ③Screening radiomics features related to endocrine resistance: 18 features such as Dependence Entropy. ④Establishing radiomics model: the machine learning model of random forest method (AUC=0.80) performed best. ⑤Radiomics model integrating clinical, pathological and conventional ultrasound features: the AUC of the clinical pathological model was 0.70, the AUC of the clinical pathological ultrasound model was 0.78, the AUC of the clinical pathological radiomics model was 0.82, and the AUC of the combined model was 0.86. Conclusions:The radiomics model established by the random forest method performs best in predicting endocrine resistance in HR-positive breast cancer. The model that integrates multiple features performs best in assessing endocrine resistance.which is expected to provide an objective basis for clinicians to predict endocrine resistance in HR-positive breast cancer.

OBJECTIVE To explore the mechanism of Xiaoyaosan in improving the abnormal glucose metabolism in chronic sleep deprivation(CSD) mice based on tyrosine hydroxylase/alpha-2a adrenergic receptor(TH/ADRA2A) signal pathway. METHODS Fifty six-week-old male C57BL/6 mice were randomly divided into two groups: 10 in the control group and 40 in the model group. The rats in the model group were deprived of sleep for 4 weeks by the method of multi-platform water environment. Fasting plasma glucose(FPG) and body mass were measured once a week for three consecutive weeks. Then, according to FPG, they were randomly divided into four groups, namely model group, guanethidine group(30 mg·kg-1·d-1) and Xiaoyaosan low and high dose groups(33.88, 101.64 g·kg-1·d-1). After grouping, continue modeling for a week. Then the drug was administered for 4 weeks. The control group and model group were treated with pure water of the same volume. Modeling continued during the administration period. On the 53rd day, blood was collected from the tail vein for the glucose tolerance test. On the 56th day, the expression of insulin(INS), noradrenaline(NE) and corticosterone(CORT) in serum was detected by ELISA. HE staining was used to observe the pathological changes of pancreatic islets. Detection of co expression of TH and INS in pancreatic tissues by immunofluorescence staining. Real-time PCR and Western blotting were used to detect the expression of ADRA2A mRNA and protein in the pancreas. RESULTS In the process of CSD modeling, compared with the initial body mass, the body mass of the model group mice decreased significantly at the end of the first week of modeling(P<0.05), and FPG increased significantly(P<0.01). After administration, compared with the control group, the glucose tolerance of the model group was significantly abnormal. The levels of NE, CORT and INS increased significantly(P<0.01), the expression level of ADRA2A mRNA and protein in the pancreas was significantly increased(P<0.01). Compared with the model group, Xiaoyaosan groups had better glucose tolerance, the levels of NE, CORT and INS decreased significantly(P<0.05), and the expression of ADRA2A mRNA and protein in the pancreas decreased significantly(P<0.05 or P<0.01). HE staining results showed that the number of cells in the islets of the model group was significantly reduced compared with the control group, and the situation was improved in all drug groups. The results of immunofluorescence staining showed that the protein content of TH in the model group increased, and the expression of TH in each group decreased after administration. CONCLUSION Xiaoyaosan can improve the abnormal glucose metabolism induced by CSD, and its mechanism may be related to the reduction of TH/ADRA2A expression.

OBJECTIVE Based on the G protein-coupled bile acid receptor(TGR5)/nucleotide binding oligomerization domain-like receptor 3(NLRP3) signaling pathway, to explore the mechanism of Huoxue Qingjieling in improving the inflammatory response of rats with nonalcoholic steatohepatitis(NASH). METHODS A total of 70 male SD rats were randomly divided into 5 groups, 20 rats in the control group, 20 rats in the model group, 10 rats in each of the atorvastatin positive drug group, the high-dose and low-dose groups of Huoxue Qingjieling. The control group was given normal feed, and the rest of the groups were given high-fat diet. Through model evaluation, it was determined that the NASH rat model was successfully established at the end of the 20th week. After successful modeling, the control group and the model group were given with normal saline by intragastric administration, the atorvastatin positive drug group, and the high and low dose groups of Huoxue Qingjieling were given corresponding drugs once a day for 4 weeks. At the end of the 24th week, the rats were killed, and the changes of body weight, wet liver weight and liver index was calculated. The serum was taken to test the triglyceride(TG), total cholesterol(TC), alanine aminotransferase(ALT), and aspartic acid aminotransferase(AST) levels by automatic biochemical analyzer. Pathological changes of liver tissues were observed by HE staining and oil red O staining. The expression levels of TGR5 and NLRP3 proteins were detected by Western blotting and immunofluorescence staining. ELISA detected the content of interleukin-18(IL-18) and interleukin-1β(IL-1β) in liver tissue. RESULTS Huoxue Qingjieling could significantly improve the general state of NASH rats. Every dose group could significantly reduce the body weight, liver wet weight and liver index of rats(P<0.01), and TG, TC content and ALT, AST activity levels of serum significantly decreased(P<0.01). The pathological results showed that Huoxue Qingjieling could significantly improve liver steatosis, inflammation and balloon-like. The expression of TGR5 protein was significantly increased(P<0.01), the expression of NLRP3 protein and the content of IL-18, IL-1β were significantly decreased(P<0.01, P<0.05). CONCLUSION Huoxue Qingjieling can significantly improve the state of NASH rats, inhibit liver steatosis and inflammation, and its mechanism may be closely related to the inhibition of TGR5/NLRP3 signaling pathway.