OBJECTIVE To analyze the influential factors on trough concentration （cmin） and area under the drug concentration time curve （AUC） of voriconazole （VRZ） in pediatric patients with thalassemia undergoing hematopoietic stem cell transplantation （HSCT）. METHODS A total of 60 pediatric patients with thalassemia undergoing HSCT who used VRZ for prevention or treatment of invasive fungal infection were collected in our hospital from January 2021 to January 2024. The plasma concentration of VRZ was measured by high-performance liquid chromatography and the AUC was calculated. The factors affecting cmin and AUC of VRZ were analyzed using multiple linear regression. RESULTS A total of 120 cases of VRZ cmin in 60 pediatric patients was obtained and 27 cases of VRZ AUC in 26 pediatric patients were obtained. The median concentration of VRZ cmin was 0.31 mg/L； 46 cases had a cmin in 0.5-5 mg/L（ 38.33%）， 2 cases had a cmin＞5 mg/L（ 1.67%）， and 72 cases had a cmin＜0.5 mg/L. The median AUC of VRZ was 11.68 mg·h/L. The patient’s body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine had significant effects on VRZ cmin （P＜0.05）. Lymphocyte count and combined use of phenytoin sodium had significant effects on VRZ AUC （P＜0.05）. CONCLUSIONS The body weight， HSCT postoperative days， lymphocyte count， and combined use of phenytoin sodium， tacrolimus or cyclosporine are independent factors affecting VRZ cmin. Lymphocyte count and combined use of phenytoin sodium are independent factors affecting VRZ AUC.

Objective:Laparoscopic surgery for cervical cancer has the advantages of little blood loss and rapid recovery,but its therapeutic effect is still controversial.This study aims to analyze the surgical procedure and clinical efficacy of tumor-free laparoscopic radical hysterectomy without a uterine manipulator for early-stage cervical cancer,and to explore the indications of laparoscopic surgery for cervical cancer. Methods:This study was a retrospective study.The data of patients who underwent radical hysterectomy for early-stage cervical cancer admitted to Hunan Provincial Maternal and Child Health Care Hospital from July 2019 to December 2021 were collected.According to 2018 the International Federation of Gynecology and Obstetrics(FIGO)clinical staging,all patients were in IA1 with lymphovascular invasion,IA2,and IB1 stage.Among them,45 patients underwent tumor-free laparoscopic radical hysterectomy without a uterine manipulator(laparoscopy group)and 16 patients underwent open surgery(open surgery group).Patients were followed up for 12-41 months.The differences between the 2 groups in terms of operative time,bleeding volume,extent of surgical resection,surgical complications,and prognosis were compared and analyzed. Results:Compared to the open surgery group,the laparoscopy group had significantly shorter operation time and less intraoperative blood loss(both P＜0.001).There were no significant differences between the 2 groups in terms of the length of excised uterosacral ligaments,cardinal ligaments,vagina,and the number of excised lymph nodes(all P＞0.05).The incidence of postoperative complications did not differ significantly between the groups(P＞0.05).No death or recurrence occurred in the 2 groups during the follow-up period.The overall survival rate and disease-free survival rate were both 100%. Conclusion:For early-stage cervical cancer with a diameter≤2 cm,tumor-free laparoscopic radical hysterectomy without a uterine manipulator is safe and feasible,and the short-term outcomes is no less than that of open surgery.

Objective:To investigate the expression level of miR-21 in patients with septic acute respiratory distress syndrome, and analyze its correlation with inflammatory factors and its value in evaluating clinical prognosis.Methods:Patients with sepsis admitted to the intensive care unit (ICU) of the First Affiliated Hospital of Hebei North University from October 2020 to March 2022 were prospectively recruited. The patients were divided into an ARDS group and a non-ARDS group according to whether ARDS occurred within 3 days after admission. The ARDS group was divided into a low-risk group and a high-risk group according to the oxygenation index, and the ARDS group was divided into a survival group and a death group according to their 28-day survival status. In addition, 50 healthy volunteers who underwent physical examination during the same period were included in the control group. The expression levels of serum miR-21 and inflammatory factors [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] were compared in each group at admission. To analyze the relationship between miR-21 expression and inflammatory factors and explore the value of miR-21 in predicting the prognosis of sepsis patients with ARDS.Results:A total of 106 patients with sepsis were included. Compared with the healthy control group, the levels of serum miR-21, TNF-α and IL-6 in the ARDS group and non-ARDS group were significantly increased (all P<0.05). Compared with the low-risk group, the levels of serum miR-21, TNF-α and IL-6 in the high-risk group were significantly increased (all P<0.05). Compared with the survival group, the serum miR-21 expression level and TNF-α and IL-6 levels in the death group were significantly increased (all P<0.05). Pearson correlation analysis showed that the serum miR-21 expression level in the ARDS group was positively correlated with IL-6 and TNF-α levels ( r=0.842, 0.697, P<0.001). ROC curve analysis showed that the AUC of serum miR-21 in predicting death from sepsis complicated with ARDS was 0.876 (95% CI: 0.761-0.942), the best cut-off value was 2.25, and its sensitivity and specificity were 92.9% and 71.7%, respectively. Conclusions:The expression level of serum miR-21 is significantly increased in patients with sepsis ARDS, is positively correlated with the level of inflammatory factors, is closely correlated with the severity and prognosis of the disease, and has great value in evaluating the prognosis of patients with sepsis ARDS.

Objective:To investigate the role of protein phosphatase 4 catalytic subunit (PP4C) in regulating hepatitis B virus X protein (HBx) levels and its effects on the biological functions of HBx, thus to provide a potential therapeutic targets for hepatitis B virus (HBV)-related hepatocellular carcinoma.Methods:In vivo and in vitro interactions between HBx and PP4C were analyzed by co-immunoprecipitation (Co-IP) and GST pull-down assay. Recombinant plasmids of PP4C and HBx were co-transfected with Lipofectamine 3000 reagents into hepatoma cells to detect the protein levels of HBx by Western blot. The half-life of HBx in the transfected cells treated with cycloheximide (CHX) were detected. The phosphorylation assay was used to evaluate the effects of PP4C on HBx phosphorylation. CCK8 assay, wound healing assay and Matrigel invasion chamber assay were used to analyze the effects of PP4C on the biological functions of HBx. Results:PP4C interacted with HBx in vivo and in vitro. PP4C overexpression significantly increased the protein level and stability of HBx and the phosphorylation assay confirmed that PP4C overexpression decreased the serine phosphorylation of HBx in hepatoma cells. PP4C overexpression enhanced the migration and invasion of hepatoma cells, but had no significant effects on the proliferation. Conclusions:The interactions between HBx and PP4C promoted the stability of HBx and ultimately enhanced the migration and invasion of hepatoma cells, and the mechanisms might be related to the decrease of HBx serine phosphorylation by PP4C. This study provided a theoretical basis for further investigation of the pathogenic mechanisms of HBx, and targeting PP4C and HBx interaction might provide insights for developing novel treatment for HBV-related hepatocellular carcinoma.

OBJECTIVE：To investigate the effect of increasing efficacy and decreasing toxicity of Limax extract （LE）on cyclophosphamide（CTX）in the treatment of hepatocellular carcinoma. METHODS ：The mice were randomly divided into normal group，model group ，CTX group （0.02 g/kg），LE low-dose ，medium-dose and high-dose groups （LEL，LEM，LEH group ，0.6，1.2，2.4 g/kg），CTX+LE low-dose ，medium-dose and high-dose combination groups （CTX+LEL，CTX+LEM，CTX+ LEH group ，the same dose as single drug group ），with 10 huangrenbin518@163.com mice in each group. Except for normal group ，other groups were inoculated with hepatoma cells H 22 in the left ar mpit to establish tumor bearing models. After 24 h of inoculation ，normal group and model group were intragastrically given normal saline ， and administration groups were intragastrically given corresponding drugs ，once a day ，for 10 days. On the second day after the last administration ，the general conditions of mice in each group were observed ；the body mass ，thymus index （LI），spleen index （SI）were measured ；the tumor inhibition rate was detected. The effect （q）of combination therapy was evaluated by King ’s formula . The counts of WBC ，RBC and PLT ，serum contents of ALT ，ALT，Scr and BUN were detected in model group ，CTX group and combination groups ，and the contents of MDA，SOD and GSH ，the levels of VEGF ，TNF-α and IL-6 in the tumor tissue were detected by colorimetry and ELISA in above groups. The protein expression of oncogenes （p53，Bcl-2 and Bax ）were detected by immunohistochemical method in model group，CTX group and CTX+LEM group. RESULTS ：The mice in the model group were in poor spirit and had symptoms of excessive drinking and eating ；although the body weight ，TI and SI were not significantly abnormal compared with normal group （P＞0.05），WBC count and AST content were significantly increased ，ALT and BUN contents were significantly decreased （P＜ 0.05 or P＜0.01）. Compared with model group ，above symptoms of mice were all improved in administration groups. The tumor weight of administration groups ，TI and SI of CTX group and TI of combination groups were decreased significantly ，but tumor weight of LEL group and LEH group ，TI and SI of LE single groups and combination groups were significantly higher than CTX group；tumor weight of combination groups were significantly lower than CTX group （P＜0.05 or P＜0.01）. The tumor inhibition rates of administration groups were 29.58％-72.08％. The q values of CTX+LEL group ，CTX+LEM group and CTX+LEH group were 1.03，0.97 and 0.86，respectively. Compared with model group ，WBC count ，AST and BUN contents of CTX group ，MDA contents of combination groups ，VEGF，TNF-α and IL-6 levels of administration groups ，the protein expression of Bcl- 2 in CTX group and CTX+LEM group were decreased significantly ；the activities of SOD and GSH of administration groups ，the protein expression of p 53 in CTX+LEM group and Bax in CTX group ，CTX+LEM group were increased significantly （P＜0.05 or P＜ 0.01）；WBC counts and AST contents of administration groups ，ALT content of CTX+LEM group ，SOD activity of CTX+LEH group and GSH activity of CTX+LEM group were all significantly higher than those of CTX group ；MDA content of CTX+LEH group，VEGF and TNF-α levels of CTX+LEM group and CTX+LEH group，IL-6 levels of administration groups were all significantly lower than CTX group （P＜0.05 or P＜0.01）. CONCLUSIONS ：LE combined with CTX can increase the anti-tumor effect，and LE can reduce the toxicity of CTX induced immunosuppression and bone marrow suppression in mice ，with effect of increasing efficacy and decreasing toxicity. The effect may be related to antioxidant stress ，inhibition of angiogenesis and secretion of inflammatory factors ，and regulation of apoptosis protein expression.

Objective:To observe the effect of exogenous hydrogen sulfide(H 2S) on the proliferation of rabbit vascular smooth muscle cell(VSMC) under high static pressure. Methods:Rabbit thoracic aorta VSMC were isolated and cultured under high static pressure(100mmHg) and divided into control group [cultured with 0.2%fetal bovine serum(FBS) and no NaHS]、10%FBS group(10%FBS and no NaHS) and NaHS group(10%FBS and 50mmol/L NaHS). VSMC proliferation was analyzed with BUDR. CSE, Calmodulin(p-CaM)and CyclinD1 protein levels of VSMC were measured by Western blotting.Results:Compared with the 10%FBS group, NaHS inhibit the proliferation of rabbit VSMC significantly (0.50±0.03 vs. 0.26±0.03, P<0.05). Compared with control group, CSE protein in the 10%FBS group decreased significantly(1.21±0.10 vs. 0.33±0.04, P<0.05) and p-CaM and CyclinD1 protein increased significantly(0.23±0.04 vs. 0.86±0.04 and 0.22±0.03 vs. 1.19±0.06, P<0.05). Compared with the 10%FBS group, CSE protein in NaHS group increased significantly(0.33±0.04 vs. 1.11±0.11, P<0.05), and the expression of p-CaM and CyclinD1 protein decreased significantly(0.86±0.04 vs. 0.26±0.05 and 1.19±0.06 vs. 0.51±0.03, P<0.05). Conclusion:Exogenous hydrogen sulfide inhibits the proliferation of VSMC under high static pressure by the CSE/H2S pathway which related to the reduction of the expression of p-CaM and CyclinD1.

OBJECTIVE: This study was performed to explore the effect of different bracket, archwire, and ligature combinations on resistance to sliding (RS) and rotational control in first-order angulation. METHODS: Three types of brackets (multi-level low friction [MLF], self-ligating, and conventional brackets) coupled with four nickel-titanium archwires (0.012, 0.014, 0.016, and 0.018-inch diameter) and two stainless steel ligatures (0.20 and 0.25 mm) were tested in different first-order angulations (0°, 2°, 4°, 6°, 8°, 10°, 15°, 20°) by using an Instron universal mechanical machine in the dry state at room temperature. RS value was evaluated and compared by one-way ANOVA. RESULTS: Under the same angulation, the RS values showed the following order: conventional brackets > MLF brackets > self-ligating brackets. The RS was the highest for conventional brackets and showed a tendency to increase. The RS for MLF brackets coupled with thinner archwires and ligatures showed a similar tendency as the RS for the self-ligating bracket. In contrast, the RS for MLF brackets coupled with thicker archwires and ligatures increased like that for conventional brackets. MLF brackets showed the greatest range of critical contact angles in first-order angulation. CONCLUSIONS: The RS in first-order angulation is influenced by bracket design, archwire, and ligature dimension. In comparison with self-ligating and conventional brackets, MLF brackets could express low friction and rotational control with their greater range of critical contact angles.
Friction ; Ligation* ; Stainless Steel ; Tooth Movement

OBJECTIVE: This study was performed to investigate buccal facial depth (BFD) changes after extraction and nonextraction orthodontic treatments in post-adolescent and adult female patients, and to explore possible influencing factors. METHODS: Twelve and nine female patients were enrolled in the extraction and nonextraction groups, respectively. Changes in BFD in the defined buccal region and six transverse and two coronal measuring planes were measured after registering pretreatment and posttreatment three-dimensional facial scans. Changes in posterior dentoalveolar arch widths were also measured. Treatment duration, changes in body mass index (BMI), and cephalometric variables were compared between the groups. RESULTS: BFD in the buccal region decreased by approximately 1.45 mm in the extraction group, but no significant change was observed in the nonextraction group. In the extraction group, the decrease in BFD was identical between the two coronal measuring planes, whereas this differed among the six transverse measuring planes. Posterior dentoalveolar arch widths decreased in the extraction group, whereas these increased at the second premolar level in the nonextraction group. The treatment duration of the extraction group was twice that of the nonextraction group. No differences were found in BMI and Frankfort horizontal-mandibular plane angle changes between the groups. BFD changes in the buccal region moderately correlated with treatment duration and dental arch width change. CONCLUSIONS: BFD decreased in adult female patients undergoing extraction, and this may be influenced by the long treatment duration and constriction of dentoalveolar arch width. However, nonextraction treatment did not significantly alter BFD.
Adult ; Bicuspid ; Body Mass Index ; Constriction ; Dental Arch ; Female* ; Humans

OBJECTIVE:To optimize the formula of Captopril timing osmotic pump tablets. METHODS:Using accumulative release rate (Q) as index, single factor test was used to investigate the effects of blocking layer coating weight gain, semipermeable membrane coating weight gain,the type of polyepoxide (PEO),the amount of PEO (3 × 105) and HPMC in drug bearing layer,the amount of PEO (7 × 106) and NaCl in booster layer on drug release of Captopril timing osmotic pump tablets. Based on single factor investigation,using comprehensive score of release behavior(L)as index,the amount of PEO(3×105)and HPMC in drug bearing layer,the amount of PEO(7×106)and NaCl in booster layer as factors,L9(43)orthogonal test was used to optimize the formula of tablet core validation test was conducted. RESULTS:The optimal formula of tablet core included PEO(3× 105)71 mg and HPMC 15 mg in drug bearing layer,PEO(7×106)61 mg and NaCl 18 mg in booster layer,coating weight gain 7％ and semipermeable membrane coating weight gain 10％ in blocking layer. The osmotic pump tablet prepared by optimized formula released after 4 h;in vitro drug release regression equation was Q=5.118t-21.441(R2=0.9956),which was in line with zero-order release characteristics. CONCLUSIONS:The optimal formula is stable,feasible and controllable in quality,and can provide reference for further development of Captopril timing osmotic pump tablets.

Objective To analyze the serum samples of young and middle-aged patients with hypertension of different syndromes and healthy patients by means of metabonomics; To confirm its biomarker; To reveal the nature of phlegm dampness retention syndrome in essential hypertension. Methods The syndrome types of 34 hypertension patients were differentiated into 14 cases of liver-fire hyperactivity syndrome group, 14 cases of phlegm dampness retention syndrome group and 6 cases of yin deficiency and yang hyperactivity syndrome group. 15 healthy volunteers were selected as control group. 1H-NMR technique combined with partial least squares-discriminate analysis (PLS-DA) method was used to look for the biomarkers. And the levels of UA, TC and TG were recorded. Results The level of UA in phlegm dampness retention syndrome group was significantly higher than the other three groups (P<0.05). The level of TC in yin deficiency and yang hyperactivity syndrome group was higher and had significantly difference with the control group (P<0.05). The level of TG in phlegm dampness retention syndrome group was higher and had significantly difference with control group (P<0.05). The metabonomics study based on the 1H-NMR method could distinguish the phlegm dampness retention syndrome group from the normal control group, liver-fire hyperactivity syndrome group and yin deficiency and yang hyperactivity syndrome group. Compared with the control group, the levels of acetone, VLDL, and LDL were significantly higher and the levels of lactate, serine, glucose, methionine, alanine were significantly lower in phlegm dampness retention syndrome group; compared with the liver-fire hyperactivity syndrome group, levels of citrate, alanine, VLDL, and LDL were significantly higher and the levels of glucose, lysine, glutamate, proline lactate were significantly lower; compared with yin deficiency and yang hyperactivity syndrome group, the level of creatinine was significantly higher. Conclusion There are lipoprotein metabolism, amino acid metabolism and glucose metabolism disorder in the young and middle-age hypertensive patients with phlegm dampness retention syndrome.