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 esta blish a method for si multaneous determination of 5 components in the branch and root of Juglans mandshurica as gallic acid ，ellagic acid ，1，6-di-O-galloyl-β-D-glucose，1，2，6-tri-O-galloyl-β-D-glucose and 1，2，3， 6-tetra-O-galloyl-β-D-glucose，and to analyze the content difference of above 5 components between the branch and root samples. METHODS：HPLC method was adopted. The determination was performed on Agilent Poroshell 120 SB-C18 column with mobile phase consisted of water （containing 0.2％ formic acid ）-acetonitrile （containing 0.2％ formic acid ）. A gradient elution was performed at a flow rate of 0.3 mL/min. The column temperature was 30 ℃ and the detection wavelength was 270 nm. The sample size was 5 μL. Independent samples t-test and partial least squares-discriminant analysis （PLS-DA）were applied for statistical analysis of 5 components. RESULTS ：The linear range of gallic acid ，ellagic acid ，1，6-di-O-galloyl-β-D-glucose，1，2， 6-tri-O-galloyl-β-D-glucose and 1，2，3，6-tetra-O-galloyl-β-D-glucose were 0.989-63.3，1.58-101，1.01-64.7，3.31-212，3.34-214 μg/mL （r≥0.997 3），respectively. RSDs of precision ，reproducibility and stability tests （12 h）were all lower than 3.2％. The average recoveries of the 5 components were 103.2％（RSD＝4.85％），99.1％（RSD＝2.80％），101.5％（RSD＝1.31％），102.9％（RSD＝ 2.73％）and 104.7％（RSD＝1.28％），respectively. The average contents of the above components in the branch of J. mandshurica were 0.296 5，0.621 1，0.562 5，3.111 7 and 3.451 3 mg/g，respectively. The average contents of above components in the root were 0.673 4，2.755 5，0.964 0，2.946 6 and 4.836 4 mg/g，respectively. The total contents of the 5 components in the branch and roo t of J. mandshurica were 8.043 2 and 12.175 9 mg/g，respectively. The contents of gallic acid ，ellagic acid and 1，6-di-O-galloyl- β-D-glucose in roots were significantly higher than those in branches （P＜0.05 or P＜0.01）. There were no significant differences in the contents of the other 2 components and the total contents of the 5 components in branches and roots （P＞0.05）. The cumulative interpretability （R 2X，R 2Y） and cumulative predictability （Q 2） of the model established by PLS-DA were 0.943，0.745，and 0.710 respectively. The model load diagram showed that the distance between the ellagic acid and the origin was the farthest ，and only variable projection importance of the content of the ellagic acid was greater than 1. CONCLUSIONS：The established method can be used for the content determination of 5 components in the branch and root of J. mandshurica . Except for 1，2，6-tri-O-galloyl-β-D-glucose，the contents of other 4 components and total contents of the 5 components in the root of J. mandshurica are higher than those of the branch. Ellagic acid is selected as the potential marker for discriminating the branch and root samples.

Objective: To study the correlation between the level of serum Chitinase-3-like protein 1 (CHI3L1) and the significant liver fibrosis and liver cirrhosis in patients with chronic liver disease, and to evaluate its diagnostic value. Methods: 165 patients with chronic liver disease were selected, liver histopathological examination was performed to detect serum CHI3L1 concentration. Four indexes of hepatic fibrosis (type III procollagen, collagen IV, laminin, hyaluronic acid), aspartate aminotransferase/platelet ratio index (APRI) and FIB-4 (fibrosis- 4) scores were based on the pathological findings of liver biopsy and compared the advantages and disadvantages of serum CHI3L1 with other methods for the diagnosis of hepatic fibrosis and liver cirrhosis. A multivariate regression analysis model was created, and receiver operating characteristic curve was analyzed. Results: The level of serum CHI3L1 increased with increase of fibrosis stage and was highest in liver cirrhosis stage. In the period of S0 to 1, the levels of S2 to 3 and S4 were 62.82 (41.40 ~ 87.20), 70.94 (48.47 to 122.60) and 141.06 (78.18 ~ 197.40), and there were statistically significant differences between the groups (P < 0.001). The area under the curve for the diagnosis of significant liver fibrosis was 0.68 (0.60 to 0.77), and 0.74 (0.65 to 0.83) for cirrhosis in CHI3L1. Multivariate regression analysis showed that CHI3L1 was an independent predictor of significant fibrosis and cirrhosis. The combined diagnostic model based on CHI3L1, collagen IV and FIB-4 scores further improved the diagnostic value. The area under the curve for the diagnosis of significant fibrosis and cirrhosis was 0.79 (0.72 to 0.86) and 0.80 (0.73 to 0.87), respectively. Conclusion CHI3L1 has a good diagnostic value in patients with chronic liver disease with significant fibrosis and liver cirrhosis. The diagnostic model in combination with other markers like Collagen IV and FIB-4 scores could further improve the diagnostic value and is worthy of further study.

OBJECTIVE:To establish a method for the determination of residuals of petroleum ether,ethanol,xylene and ace-tic acid in ecabet sodium crude drug. METHODS:Capillary GC was performed on the column of PGE-20M capillary column at the flow rate of 1.7 ml/min,detector was hydrogen flame ionization detector,carrier gas was nitrogen with high purity,column temper-ature was 45 ℃,maintaining 4 min,it increased to 80 ℃ with rate of 10 ℃/min,then increased to 135 ℃ with rate of 30 ℃/min,maintaining 3 min,the injection mode was direct injection,inlet temperature was 250 ℃,and the volume injection was 1.0 μl. RESULTS:The mass concentration was 0.050-1.952 g/L for petroleum ether,0.050-1.941 g/L for ethanol,0.024-0.948 g/L for xy-lene and 0.050-1.947g/L for acetic acid(r=0.999 1-0.999 7);RSDs of precision,stability and reproducibility tests were no more than 1.7%;recoveries were 99.3%-101.0%(RSD=0.7%,n=9),102.3%-103.7%(RSD=0.4%,n=9),101.2%-102.1%(RSD=0.3%,n=9) and 100.3%-102.2%(RSD=0.6%,n=9),respectively. CONCLUSIONS:The method is simple and accurate,and can be used for the control of residual of organic solvents in ecabet sodium crude drug.

Objective: To explore the correlation between glycosylated hemoglobin (HbA1c) level and severity of coronary artery disease in patients with coronary heart disease (CHD). Methods: Clinical data of 515 patients, who hospitalized in department of cardiology and received coronary angiography (CAG) examination, were analyzed. According to CAG results, they were divided into CHD group (n=370) and normal CAG group (n=145); according to HbA1c level, CHD patients were further divided into HbA1c<7% group (n=282) and HbA1c≥7% group (n=88), according to SYNTAX score, they were divided into SYNTAX score low risk group (n=181, 1~22 scores), intermediate risk group (n=125, 23~32 scores) and high risk group (n=64, ≥33 scores). HbA1c level was compared and analyzed among all groups. Results: Coronary SYNTAX score of HbA1c≥7% group was significantly higher than that of HbA1c<7% group [(25.6±9.97) scores vs. (20.92±10.26) scores, P<0.01]. HbA1c levels in high risk and intermediate risk groups were significantly higher than those of normal CAG group and low risk group [(8.74±0.83) scores, (7.74±0.62) scores vs. (5.12±0.49) scores vs. (5.68±0.59) scores], P<0.01 all, and that of low risk group was significantly higher than that of normal CAG group, , P<0.01 all. Pearson correlation analysis indicated that HbA1c level was positively correlated with coronary SYNTAX score (r=0.764, P<0.01). Conclusion: Glycosylated hemoglobin level is positively correlated with severity of coronary artery disease. Its level in those with higher SYNTAX score is significantly higher than those with low SYNTAX score.

Clostridium cellulolyticum, as one of obligate anaerobic bacteria capable of secreting cellulosome, has not been efficiently cultured due to its strict requirement of growing conditions. In this study, culture conditions of C. cellulolyticum were optimized using response surface methodology. Plackett-Burman design was first used to screen the dominant impact factors for the growth of C. cellulolyticum, which were determined as yeast extract concentration, cellobiose concentration and culture temperature. The steepest ascent path design was then applied to gain the suitable range close to the optimal culture conditions for obtaining high cell density. The central composite design and the response surface analysis were finally used to determine the optimal levels of the influential factors, which were 3 g/L for yeast extract concentration, 7 g/L cellobiose concentration and 34 degrees C for culture temperature. The optimized medium was used for flask culture, and OD600 of C. cellulolyticum was increased from 0.303 to 0.586. With a pH-controlled fermentor at batch mode, OD600 reached 3.432, which was 2.8 times higher than elsewhere reported. These results support further study on the high-density culture of C. cellulolyticum and its application.
Bacteriological Techniques ; methods ; Clostridium cellulolyticum ; growth & development ; Culture Media ; Population Density

Objective This study aims to investigate the relationship between the dental and basal arch forms of patients with skeletal class Ⅱ malocclusion using three-dimensional virtual models and to generate the best-fit curve for these arch forms. Methods The mandibular dental casts of 35 skeletal class Ⅱ patients were taken prior to treatment and were laser scanned. The facial axis (FA) points, which were used to represent the dental arch, and the WALA points, which were used to represent the basal bone, were identified for each tooth from the right first molar to the left first molar. The Pearson corre-lation coefficients between the intercanine and intermolar widths at the FA and WALA points were determined. Finally, the best-fit curves were generated using the fourth-degree polynomial equation to represent the arch forms. Results A strong correlation was found between the FA and WALA intermolar widths (r=0.873). However, a moderate correlation was observed between the FA and WALA intercanine widths (r=0.534). The difference between the intermolar widths at the FA and WALA points was significant (P<0.01). No statistically significant difference was found between the intercanine widths (P=0.481). The radii of curvature of the FA and WALA curves in the anterior teeth area were 15.194 and 20.250, respectively. The re-gression coefficients of the FA and WALA curves were calculated as R2=0.912 and 0.947, respectively. Conclusion For skeletal class Ⅱ malocclusion patients, the FA and WALA dental intermolar widths showed strong correlation, whereas the FA and WALA intercanine widths exhibited moderate correlation. The FA points were located more labially in the anterior teeth area but more lingually in the posterior teeth area. No statistically significant difference was found between the intercanine FA and WALA widths. The difference between the intermolar widths at the FA and WALA points was significant. The radii of curvature of the FA curve was larger than that of the WALA curve in the anterior teeth area.

Objective To study the mechanism of paraquart-induced renal injury in rats,the expression of heine oxygenase-2(HO-1) and inducible nitric oxide synthase (iNOS).Methods 84 adult healthy Spragne-Dawley (SD) rats (female and male in half) were randomly divided into two groups,the control group (group A,n=42) and the paraquart group (group B,n=42).The rats in group B were treated with paraquart (25 mg/kg) intraperitoneally,the rats in group A were treated with the same dose of normal saline.Its histopathological change,the expression of HO-1,iNOS and evaluate the mRNA expression of HO-1 were observed.Results ①In group A,the tissue structure was clear without abnormal.In group B,there were obvious lesions in the renal tubule of cortical part,including cellular swelling,the canula narrow,the mesenchymal congestion and edema.These pathologic changes gradually reached the peak on the 1st day,and did not relieved till the end ofthis study.②In group A,there was no or weak expression of iNOS.At the 3rd hour,the expressions of iNOS in group B were observed in the kytoplasm of renal tubular epithelial cell and glomemlar endothelial cell of cortical part.It reached the peak on the 1st day and continued at a high level after that.③ In group A,there was no or weak expression of HO-1 and HO-1 mRNA.At the 3rd hour,the expressions of HO-1 in group B were observed in the membrane and kytoplasm of renal tubular epithehal cell of cortical part,immunohistochemistry score(IHS) was higher,the expression of HO-1 mRNA increased,there was a statistical significance between group B and group A(P<0.05).It reached the peak on the 1st day,and then decreased,there were 110 statistical difference between group B and group A on the 5th day(P>0.05).Conclusions HO-1 and iNOS ale involved in the procedures of renal injury,but its mode of action and regulating path still need further study.

Objective To explore the effect of long-term depleted uranium (DU)ingestion on testosterone production in rats, and its involvement mechanism. Methods Male and female rats (F0 and F1 respectively) for 160 days, respectively. The contents of testosterone (T), luteinizing hormone (LH), and follicle stimulating hormone (FSH) in serum were detected in 20 months of F0 generations, and 15 months of F1 generations. RT-PCR was used to analyze the levels of StAR mRNA and P450scc mRNA. Results Compared with the normal control group, the testosterone contents in exposed F0 and F1 generations increased, the lowest was 51.73 U/L, but those of LH and FSH decreased. The expression of StAR mRNA in the low-doze group of F1 generation (StAR/β-actin = 1.35) was up-regulated, down-regulated for other groups.compared with the normal control group (P450scc/β-actin = 0. 313), the expression of P450scc mRNA in the low- and high-dose groups of F0 generation were decreased (P450scc/β-actin = 0.21), and those in the low- and high-dose groups of F1generation were increased (P450scc/β-actin = 0.623) (P ≤ 0.01). Conclusion Long-term DU exposure inhibit the male reproduction by intervening the sexual hormone production through down-regulated the expression of StAR mRNA and P450scc roRNA.