Objective To discusse the influence of permeating perfluoropentane drops-encapsulated mesoporous silica nanocapsules (MSNC-PFP) on HIFU surface ablation in vitro bovine liver.Methods Fifity bovine liver tissues were divided into 5 groups:Control group,0.25 mg/ml group,0.50 mg/ml group,1.00 mg/ml group,2.00 mg/ml group according to the concentration of MSNC-PFP.The synergistic agent was injected along the ablation line path under the guiding of ultrasound.The surface ablation model was structured by 6 coagulation necrosis side by using HIFU linear scanning,inner region without melting,and the ultrasonographic changes were observed in the melt area.The coagulation necrosis range was assessed by TTC staining,and necrosis degree was observed by HE staining.The coagulation necrosis volume was measured,the coverage index (CI),external volume index (EI),energy efficiency factor (EEF) were used to evaluate the ablation effect in each group.Results The MSNC-PFP more than 1.00 mg/ml was shown as strong echo in ultrasonic image,fade after 3-5 min.The grey value was changed in HIFU ablation area related to the concentration of MSNC-PFP.The total ablation volume of 0.50 mg/ml group,1.00 mg/ml group,2.00 mg/ml group were more than control group,the EEF was lower than that of the control group (all P＜0.01).The CI and EI of 1.00 mg/ml group and 2.00 mg/ml group were higher than those of the other group (all P＜0.01).The coagulation necrosis became complete when the concentration of MSNC-PFP above 0.50 mg/ml.Conclusion MSNC-PFP can increase the volume of coagulation necrosis,decrease the EEF and increase the efficiency of HIFU surface ablation of bovine liver in vitro.

Objective To study the changes of CDH1 gene promoter CpG island methylation and its clinical significance in patients with esophagus and stomach double primary carcinoma(ESDC).Methods The expression of CDH1 gene methylation in cancerous tissues and adjacent cancerous tissues in 18 cases of ESDC were detected using methylation-specific PCR method. Results Eighteen patients were endoscopically diagnosed as ESDC between Jan. 2007 and Sep. 2009 in the 4th Hospital Affiliated to Hebei Medical University. The positive methylation of CDH1 gene in tissues of esophageal squamous cell carcinoma (ESCC)and adjacent cancer were 66.7% and 33. 3%, respectively, with significant difference (χ2= 4. 167, P = 0. 031). Whereas the positive methylation of CDH1 gene in tissues of gastric carcinoma (GA) and adjacent cancer were 77.8% and 44.4%, respectively, without statistical difference (χ2=1.786, P= 0. 180). There was no significant difference (P=0. 500) in positive rate of CDH1 gene methylation between ESCC tissues and GA tissues in same individual with ESDC. For 18 patients with ESDC, consistent change of CDH1 methylation in tissues of two kinds of cancers was found in 16 patients with a total agreement of 88.9 % (positive agreement of 66.7 % and negative agreement of 22. 2%). Statistical analysis showed a significant correlation between two groups (P = 0. 005). Conclusion In patients with ESDC, there is a high consistency of CDH1 methylation change, between ESCC and GA,which suggests that two kinds of cancer may have similar risk factors and molecular mechanisms.

Objective:To explore the method of establishing a modified demyelination and myelination regeneration model induced by dicyclohexanone oxalyl dihydrazone (CPZ) in mice with multiple sclerosis (MS), and to analyze the image markers of demyelination and myelination regeneration in mouse MS model.Methods:After the intragastrically administered with sodium carboxymethyl cellulose (CMCNa) for one week, a total of 30 C57BL/6 male mice were randomly divided into the control group ( n=10), the demyelination group ( n=10), and the remyelination group ( n=10). The mice of the control group were immediately performed MR scanning and pathological specimen obtaining; the mice in the demyelination group were administered with intragastrical CPZ-CMCNa once a day for 6 weeks for inducing demyelination, then received MR scanning and specimen obtaining with the same protocols used in control group; the mice in the remyelination group were administered with intragastrical CPZ-CMCNa once a day for six weeks for demyelination, then CPZ was withdrawn and normal diet was given for another four weeks. Then MR scanning and specimen obtaining were performed with the same protocols used in the other two groups. Regions of interest (ROIs) were set at the rostrum of corpus callosum (rCC), the bilateral normal appearing white matters (NAWM) of the rostrum of corpus callosum, and the bilateral cerebral cortex (Cx). The normalized T 2WI (T 2-normalized), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were compared among the three groups by one-way ANOVA. Results:The demyelination and remyelination mice model of MS were successfully established. The T 2-normalized values of rCC in control group, demyelination group and remyelination group were 0.47±0.03, 0.72±0.04, 0.54±0.04, respectively, with statistically significant difference found ( F=90.511, P<0.05). Post-hoc multiple comparisons showed significant differences among those groups ( P<0.05). There was no significant difference of T 2-normalized value in NAWM and Cx among the three groups ( P>0.05). Moreover, there were significant differences in the FA values (0.36±0.04, 0.29±0.03, and 0.32±0.05), the MD values [(0.572±0.015), (0.598±0.034), and (0.626±0.043)×10 -3 mm 2/s], the AD values [(0.79±0.04), (0.77±0.06), and (0.83±0.04)×10 -3 mm 2/s], and the RD values [(0.46±0.02), (0.51±0.03), and (0.53±0.05)×10 -3 mm 2/s] of rCC of the control group, the demyelination group, and the remyelination group (all P<0.05). Significant difference was found in FA values between the demyelination group and the control group ( P<0.05), and in MD values between the remyelination group and the control group ( P<0.05), as well as in AD values between the remyelination group and the demyelination group ( P<0.05). There were also significant differences in RD values between the remyelination group and the control group, and the demyelination group and the control group (all P<0.05). However, no significant difference was found in all diffusion tensor imaging (DTI) metrics of NAWM and Cx among the three groups (all P>0.05). The LFB-eosin staining showed that the myelin sheath of rCC was lost in the demyelination group, and the rCC was partially regenerated and repaired in the remyelination group. Conclusion:The modified CPZ-CMCNa model can selectively induce demyelination and remyelination of rCC, and the changes of demyelination and remyelination of rCC in the modified CPZ-CMCNa model can be quantitatively detected by T 2WI combined with DTI, which might provide related theoretical basis for the study on dynamic changes of MS lesions.

Objective: To explore whether social support has a moderating effect on the relationship between negative emotions including depression, anxiety, stress with suicidal behaviors, and to provide reference for the suicide prevention among college students. Methods: Three universities were selected in Qinghai, Ningxia and Xinjiang province, and 4 893 college students were selected using cluster sampling method. The Social Support Scale, Depression-Anxiety-Stress Scale(DASS) and Suicidal Behavior Questionnaire-Revised self-evaluation questionnaires were used to collect data. Hierarchical linear regression model was employed to explore the moderating effect of social support. Results: A total of 4 893 college students completed full questionnaires and included in the final analysis. Among them, 738(15.08%) were under high risk of suicidal behaviors. The regression model showed that DASS score was positively associated with suicidal behavior (β=0.31, P<0.01), and social support was negatively associated with suicidal behavior (β=-0.08, P<0.01); Additionally, the interaction between social support and DASS negatively correlated with suicidal behavior (β=-0.05, P<0.01). Conclusion Social support may have buffering effects on the relationship between negative emotions (depression, anxiety and stress) and suicidal behaviors.

Objective To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People′s Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m2, (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m2, (6.7±1.6) mmol/L, (6.1± 1.2) mmol/L; (22±3) kg/m2, (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM ( OR=2.799, 95% CI :1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.

Objective:To investigate the curative effect of endoscopic cyclophotocoagulation combined with trabeculectomy for primary open angle glaucoma.Methods:From January 2020 to May 2021, 30 eyes of 30 patients with advanced primary open angle glaucoma with cataract who underwent endoscopic cyclophotocoagulation combined with trabeculectomy in the Municipal Hospital Affiliated to Xuzhou Medical University were retrospectively analyzed. The preoperative best corrected visual acuity, preoperative intraocular pressure (IOP) and numbers of anti-glaucoma medication were recorded. IOP, numbers of anti-glaucoma medication at 1 day, 3 months, 6 months and 1 year after operation, postoperative complications, the numbers of absolute success and qualified success were recorded.Results:All cases were followed up for 1 year. The best corrected visual acuity improved by more than one line in 26 eyes at 1 year after operation. Preoperative visual acuity was maintained in 3 eyes visual acuity decreased in 1 eye. The IOP and numbers of anti-glaucoma medication at 1 day, 3 months, 6 months and 1 year after operation were significantly different from those before operation ( P<0.01). At 1 year after operation, 8 patients were qualified successful and 17 patients were absolutely successful. Early hyphema in 30 eyes, transient ocular hypertension in 3 eyes ciliary body detachment in 0 eyes, corneal edema in 9 eyes, and anterior chamber exudation in 8 eyes. Conclusions:In this small sample size of study with follow-up for 12 months, the results showed that endoscopic cyclophotocoagulation combined with trabeculectomy in the treatment of advanced open angle glaucoma has good preliminary efficacy and safety. However, a large sample of cases is still needed to further study its long-term safety and efficacy.

Autophagy is a lysosome-mediated catabolic process that captures and degrades dysfunctional organelles and useless proteins during cellular stress process， which plays a dual role in cervical cancer. In the early stage of cervical cancer， autophagy inhibits the occurrence and development of cervical cancer by prohibiting the accumulation of oncogenic p62 protein. In the advanced stage of cervical cancer， inhibition of autophagy of cancer cells enhances the sensitivity of cancer cells to chemotherapeutic drugs， thus inhibiting their proliferation. In recent years， the research on Chinese medicine monomers regulating autophagy in the treatment of cervical cancer has attracted extensive attention from scholars at home and abroad. Chinese medicine monomers regulate the autophagy of cervical cancer cells through multiple pathways and multiple targets， so as to increase the apoptosis rate and reduce the resistance of cancer cells to chemotherapeutic drugs. Therefore， this paper reviewed the mechanism of Chinese medicine monomers in inhibiting cervical cancer through autophagy， expecting to find new breakthroughs in the discovery and development of preventive and therapeutic drugs for cervical cancer. By reviewing the literature， it was found that in the early stage of cervical cancer， Chinese medicine monomers activated autophagy to promote apoptosis of cancer cells， and the main mechanism was to increase lysosomal membrane permeability and chemotherapeutic sensitivity and activate intact autophagy flow. In the advanced stage of cervical cancer， inhibition of autophagy reduced the sensitivity of cancer cells to chemotherapy drugs by inhibiting the formation of autophagosomes and autolysosomes. The treatment of cervical cancer by Chinese medicine monomers regulating autophagy has achieved certain effect， but there are few clinical experimental studies and lack of reliable clinical theoretical basis. Therefore， it is essential to carry out more clinical experimental studies on Chinese medicine monomers regulating autophagy to treat cervical cancer， thus finding more reliable theoretical basis for the treatment of tumors.

AIM: To investigate the guiding role of individualized medication adjustment based on CYP2C19 metabolic typing in the treatment of ischemic stroke with clopidogrel, and to provide reference for clinical individualized medication. METHODS: The total of 80 patients with ischemic stroke were divided into the individualized drug instruction group with gene detection (n=40) and the control group without gene detection (n=40) according to whether they received CYP2C19 gene detection. According to the metabolism of CYP2C19, the individualized medication instruction group was divided into slow metabolic type, intermediate metabolic type, fast metabolic type and ultra-fast metabolic type. Patients with fast and ultra-fast metabolites were given clopidogrel dose of 75 mg once a day. Patients with intermediate metabolic type were given double clopidogrel dose of 150 mg once a day. Patients with slow metabolism were given tigrillo dose of 90 mg twice a day or aspirin dose of 100 mg once a day. The control group received 75 mg clopidogrel once a day. All patients enrolled in the groups were followed up for 3 months by outpatients or telephone. The incidence of vascular events and mRS scale scores were compared between the two groups. RESULTS: The incidence of vascular events in the individualized drug instruction group was significantly lower than that in the control group, and the incidence of mRS score(0-1) was significantly higher than that in the control group, with statistically significant differences (P<0.05). CONCLUSION: The individualized medication for patients with ischemic stroke by CYP2C19 gene detection can significantly reduce the incidence of adverse vascular events and improve the prognosis and living ability of patients.

OBJECTIVE To provide a reference for the safe use of drugs in patients with complex venous thromboembolism （VTE） and acute renal insufficiency. METHODS Clinical pharmacists participated in the management of anticoagulant therapy for a patient with complex VTE complicated with acute renal insufficiency， and evaluated the patient as high-risk thrombosis and bleeding based on their medical history， laboratory test results， etc.； combined with the complexity of thrombosis and renal insufficiency， clinical pharmacists suggested that enoxaparin sodium should be used in the acute stage of thrombosis （5 to 21 days after onset）， and then warfarin should be adopted for oral anticoagulation treatment. Because the patient’s anticoagulation was not up to the standard （the target range of the international normalized ratio was 2-3）， clinical pharmacists suggested increasing the warfarin dose， detecting the warfarin metabolism genotype， and adjusting the warfarin dose according to the genotype； at the same time， clinical pharmacists developed an anticoagulation monitoring plan to ensure the safety of anticoagulation treatment. RESULTS Doctors had adopted all the recommendations of clinical pharmacists. The patient did not experience adverse events such as bleeding or worsening of thromboembolism during anticoagulation in the hospital. When the anticoagulation met the standards， the patient was allowed to be discharged with medication. CONCLUSIONS By participating in the anticoagulation treatment management of patients with complex VTE and acute renal insufficiency， clinical pharmacists have assisted doctors in formulating personalized anticoagulation plans to promote the compliance with the anticoagulation treatment standard and ensure the safety and effectiveness of medication for patients.

Objective: To explore the relationship between hemoglobin (Hb) level during the first trimester of pregnancy and gestational diabetes mellitus (GDM). Methods: A total of 1 276 participants, who underwent scheduled prenatal examination and normal singleton delivery at the Fifth People's Hospital of Shanghai and Hospital of Intergrated Chinese and Western Medicine in Minhang District, from January 2016 to May 2018 were included. There were 99 cases of GDM (GDM group) and 1 177 cases of normal (control group) pregnant women.Based on the serum Hb level during the first trimester of pregnancy, participants were divided into three groups, 236 cases of low Hb level group (Hb<110 g/L), 868 cases of normal Hb level group (110 g/L≤Hb<130 g/L), and 172 cases of high Hb level group (Hb≥130 g/L). Maternal clinical data were collected, including Hb level during the first trimester of pregnancy, three-point blood glucose (BG) of oral glucose tolerance test (OGTT) and fasting insulin during the second trimester of pregnancy. Homeostasis model assessment of insulin resistance index (HOMA-IR) and homeostasis model assessment of pancreatic β cell function index (HOMA-β) were used to evaluate insulin resistance and pancreatic β cell function. Results: (1) Hb level during the first trimester of pregnancy in GDM group was significantly higher than that in control group [(123±10),(119±11) g/L, P<0.05]. There were no significant difference in gravidity, parity, index of liver and renal function (all P>0.05). (2) Pre-pregnancy body mass index (BMI), 1-hour BG and 2-hour BG of OGTT were significantly increased in the high Hb level group during the first trimester of pregnancy, which were (23±4) kg/m², (7.3±2.0) mmol/L, and (6.5±1.4) mmol/L (P<0.05), respectively. The pre-pregnancy BMI, 1-hour BG and 2-hour BG of the normal or low Hb level group were (22±3) kg/m², (6.7±1.6) mmol/L, (6.1±1.2) mmol/L; (22±3) kg/m², (6.5±1.5) mmol/L, (5.9±1.1) mmol/L, respectively. There were no statistically significant difference in levels of fasting blood glucose, fasting insulin, HOMA-IR and HOMA-β within 3 groups (all P>0.05). (3) In the high Hb level group, prevalence of pregnancy overweight or obesity and GDM were the highest, which were 37.2%(64/172) and 15.1%(26/172), respectively; the differences were statistically significant (all P<0.05). (4) The serum Hb level in the first trimester was positively related with pre-pregnancy BMI (r=0.130, P<0.05), 1-hour BG (r=0.129, P<0.05), 2-hour BG (r=0.134, P<0.05), fasting insulin (r=0.096, P<0.05), and HOMA-IR (r=0.101, P<0.05).Logistic regression indicated that Hb≥130 g/L during the first trimester of pregnancy was an independent risk factor for GDM (OR=2.799, 95%CI: 1.186-6.604; P<0.05). Conclusion The high level of Hb (Hb≥130 g/L) during the first trimester of pregnancy is associated with GDM.