OBJECTIVE To compare the predictive accuracy and clinical applicability of four vancomycin individualized dosing tools （SmartDose， ClinCalc， Gulou， Pharmado） and provide a basis for rational clinical medication use. METHODS A retrospective cohort study was conducted， enrolling 479 adult patients who received vancomycin therapy and underwent steady-state trough concentration monitoring in Zhongshan Hospital， Fudan University （Xiamen Branch） from January 1， 2022， to June 30， 2024. The predictive accuracy of each tool was evaluated using indicators， such as mean error （ME）, mean absolute error （MAE）， mean percentage error （MPE）， mean absolute percentage error （MAPE）， the proportion of patients with an absolute percentage error （APE） of less than 30%， the 95% limits of agreement， and the overall relative percentage difference between predicted and measured values. Using indicators such as accessibility， patient management， and recommendation of multiple treatment options， the clinical panxso@163.com applicability of the tools for all patients was evaluated； using the discrepancy in accuracy between the predicted and actual measured blood drug concentrations as an indicator， the clinical applicability was assessed for patients in different renal function subgroups （hyperfunction， normal， mild impairment， moderate impairment， and severe impairment）. RESULTS In terms of accuracy， SmartDose demonstrated the best overall performance with an MAPE of 46.40% and a proportion of APE ＜30% （46.56%）. Bland-Altman analysis indicated that SmartDose had the smallest overall relative percentage difference （－7.25%）， although the 95% limits of agreement were broad for all tools， with differences between the upper and lower limits exceeding 200%. In terms of applicability， all four dosing tools were freely accessible and demonstrated good availability； SmartDose and Pharmado provided the most comprehensive solutions， offering features such as patient management， multiple regimen recommendations， and drug concentration-time curve plotting. Stratified analysis based on renal function revealed that Pharmado showed optimal prediction for hyperfiltration patients （mean difference： 0.11 mg/L）. SmartDose and ClinCalc showed relatively better performance in normal and mild renal impaiment （mean difference： 0.37， 0.51 mg/L and －1.13， －1.33 mg/L，respectively）. SmartDose performed best in moderate renal impairment （mean difference： －2.60 mg/L）. Pharmado and Gulou had smaller prediction biases in severe renal impairment （mean differences： 1.52 mg/L and －0.23 mg/L， respectively）. CONCLUSIONS The four individualized dosing tools demonstrated limited accuracy in the initial prediction of vancomycin concentrations. Among them， SmartDose demonstrates the highest overall prediction accuracy and possesses comprehensive clinical management features. It is recommended that Pharmado be preferred for patients with renal hyperfiltration； SmartDose or ClinCalc can be used for patients with normal or mildly impaired renal function； SmartDose is recommended for patients with moderately impaired renal function； Pharmado or Gulou may be considered for patients with severely impaired renal function.

Threatened abortion is a common disease of obstetrics and gynecology and one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in TCM obstetrics and gynecology， Western medicine obstetrics and gynecology， and pharmacology to deeply discuss the advantages of TCM and integrated Chinese and Western medicine treatment as well as the medication plans for threatened abortion. After discussion， the experts concluded that chromosome， endocrine， and immune abnormalities were the key factors for the occurrence of threatened abortion， and the Qi and blood disorders in thoroughfare and conception vessels were the core pathogenesis. In the treatment of threatened abortion， TCM has advantages in preventing miscarriages， alleviating clinical symptoms and TCM syndromes， relieving anxiety， regulating reproductive endocrine and immune abnormalities， personalized and diversified treatment， enhancing efficiency and reducing toxicity， and preventing the disease before occurrence. The difficulty in diagnosis and treatment of threatened abortion with traditional Chinese and Western medicine lies in identifying the predictors of abortion caused by maternal factors and the treatment of thrombophilia. Recurrent abortion is the breakthrough point of treatment with integrated traditional Chinese and Western medicine. It is urgent to carry out high-quality evidence-based medicine research in the future to improve the modern diagnosis and treatment of threatened abortion with TCM.

Objective:To screen the incidence of proteinuria in rural areas of Shanxi province and construct a risk prediction model of proteinuria based on machine learning algorithm.Methods:It was a cross-sectional investigation study. The residents ≥30 years old in rural areas of Shanxi province from April to November 2019 were screened by multi-stage stratified sampling method, and data from questionnaire surveys, physical examinations, and laboratory examinations were collected. Urine albumin/creatinine ratio ≥30 mg/g was defined as proteinuria, and the incidence of proteinuria was calculated. Subjects were divided into proteinuria group and non-proteinuria group. The machine learning binary classification model of proteinuria and non-proteinuria was constructed based on the stackable integrated logistic regression algorithm (SE-LR), logistic regression, support vector machine, decision tree, random forest and extreme gradient lift algorithms, respectively. The area under the receiver operating characteristic curve, accuracy, recall, and F1 weights were used to evaluate the predictive efficiency of the comparison models. Finally, the importance of the predictive features of the model with the best overall performance was ranked.Results:There were 8 869 rural residents included in the study, aged (58.59±9.49) years old, with 3 872 males (43.66%) and 4 997 females (56.34%). The prevalence of proteinuria in rural areas of Shanxi province was 13.49% (1 196/8 869). Blood pressure, pulse, body mass index, waist circumference, proportion of obesity or overweight, proportion of hypertension, proportion of moderate to severe salt intake, glycosylated hemoglobin, uric pH value, urinary specific gravity, proportion of positive urinary occult blood, proportion of positive urinary glucose, proportion of positive urinary ketone body, proportion of urinary red blood cell count ≥5/μl, proportion of urinary white blood cell count ≥10/μl and urinary α1 microglobulin in the proteinuria group were all higher than those in the non-proteinuria group (all P<0.05). The proportions of lack of exercise and drinking history in the proteinuria group were lower than those in non-proteinuria group (both P<0.05). The overall performance of SE-LR model was the best, with the area under the curve (0.736, 95% CI 0.719-0.746) slightly lower than that of the logistic regression model (0.745, 95% CI 0.680-0.762), and the highest accuracy (0.844), recall rate (0.621) and F1 weighting value (0.801). In the SE-LR model, the orders of importance of the top 10 features were urinary α1- microglobulin, urinary occult blood, urinary sugar, uric acid basicity, smoking history,overweight or obesity, body mass index, total cholesterol, glycosylated hemoglobin and hypertension. Conclusions:The prevalence of proteinuria is high in rural areas of Shanxi province. The risk prediction model of proteinuria established by machine learning algorithm can predict the risk of proteinuria and identify its risk factors, which can provide a scientific basis for disease prevention, intervention, and treatment in the community and clinic to a certain extent.

The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.
Escherichia coli/genetics* ; Glutamine ; Zeolites/chemistry* ; Amino Acids

Objective:To analyze the indications for invasive prenatal diagnosis in the third trimester and summarize the pregnant outcome.Methods:Clinical data of 121 women who underwent invasive prenatal diagnosis in the third trimester in the prenatal diagnostic center of the First Medical Center of Chinese PLA General Hospital from January 2016 to December 2020 was retrospectively analyzed. Different genetic diagnostic methods were used according to different indications. Indications and results of prenatal diagnosis, as well as the complications within two weeks after the invasive procedure, pregnancy outcome, and neonatal follow-up of all the participants were described.Results:Among the 121 cases, 107 cases underwent amniocentesis, seven underwent percutaneous umbilical blood sampling, and seven had both procedures performed at the same time (one underwent thoracocentesis at the same time). Newly identified ultrasound abnormalities in the second and third trimesters were the main indications for prenatal diagnosis, accounting for 99.2%(120/121), of which short limbs and fetal growth restriction accounted for 25.0% (30/120) and 20.0% (24/120), respectively. Genetic abnormalities and congenital diseases were detected in 20 cases with a detection rate of 16.5%(20/121). Among them, there were nine cases of achondroplasia, five cases of pathogenic copy number variations, one case of achondroplasia with pathogenic copy number variation, one trisomy 18, one 47,XXX, one tetrasome mosaicism of 12p, one de novo WTX c. 1072(Exon2) C>Tp.R358X heterozygous mutation, and one fetal hypoproteinemia. In addition, six cases with copy number variation of unknown significance (VUS) were detected, noting for a detection rate of 5.0%(6/121). Among the 20 cases with abnormal detection, 15 were terminated, two delivered prematurely before obtaining the prenatal diagnosis results, one underwent cesarean section before obtaining prenatal diagnostic results and two continued the pregnancies. In the six cases with VUS, one was terminated and the other five continued the pregnancy. Only one case had preterm premature rupture of membranes 2 d after amniocentesis and the incidence rate of complications after all kinds of invasive procedures was 0.8% (1/121). During the neonatal follow-up, postnatal whole exome sequencing revealed monogenetic disorder in two cases with normal prenatal diagnostic results; the patient with 12p chimerism had developmental delay; the one with WTX mutation deceased on the day of born; the rest newborns developed normally. Conclusions:As a relatively safe method, invasive prenatal diagnosis in the third trimester is of great importance and value in reducing the miss diagnostic rate of fetuses with severe genetic diseases and birth defects. The appropriate application of prenatal whole exome sequencing could further help to decrease the miss diagnostic rate of monogenetic disorder.

Objective:To construct endocrinology nursing subspecialty model and explore its clinical effect.Methods:In December 2018, the organization structure of endocrinology nursing subspecialty was constructed in the Drum Tower Hospital Affiliated of Nanjing University Medical School and applied in clinic. In this model, the data of 2018 were taken as the data before application and the data of 2020 were taken as the data after application. The comprehensive ability of nurses, nurse satisfaction, related nursing workload and scientific research ability of nurses were compared before and after the application of the model.Results:After the application of subspecialty nursing mode, nurses′ comprehensive ability score was (92.00 ± 2.36) points. Compared with (84.25 ± 3.24) points before implementation, the difference was statistically significant ( t=-9.46, P<0.01); nurses′ satisfaction evaluations including specialty development (7.92 ± 1.41), self-quality improvement (8.00 ± 1.69), work pressure (6.42 ± 2.67), salary and welfare (3.96 ± 0.85), compared with (5.79 ± 2.31), (6.17 ± 2.82), (8.33 ± 1.50), (2.88 ± 1.59) before implementation, the difference was statistically significant ( t values were -3.86--2.73, all P<0.05). The annual workload of related nursing increased and the scientific research ability of nurses was improved. Conclusions:The application of endocrinology nursing subspecialty mode is beneficial to improve nurses′ comprehensive ability of clinical work, improve the level of specialized nursing, improve the quality of nursing service and promote the improvement of economic benefits, which is worthy of clinical promotion.

Objective:To investigate the role and mechanism of Nod-like receptor protein 3 (NLRP3) in chronic kidney disease (CKD)-related neointimal hyperplasia (NH) of vessels.Methods:Wild type C57BL/6J male mice were randomly divided into normal control group ( n=6) and experimental group ( n=18), by removal of 5/6 kidney and ligation of left common carotid artery to establish a NH model. After established successfully, the mice in NH experimental group were randomly divided into NH model group, NLRP3 inhibitor group, and drug control group ( n=6/group). C57BL/6J male mice with NLRP3 gene knockout group did not do any treatment after the establishment of NH model. After 3 weeks of feeding, the blood and vascular tissue samples of mice were collected. The pathological changes of vascular tissue samples in mice were observed by hematoxylin-eosin staining. The expressions and localization of NLRP3-related protein were observed by immunofluorescence staining. The expression of NLRP3 mRNA in vascular tissue was detected by quantitative real-time PCR. The activity of caspase-1 in vascular tissue was measured by colorimetric method. Human aortic smooth muscle cells (HASMCs) were treated with 10% uremic serum to simulate the body's internal environment during the uremic phase. NLRP3 small interfering RNA (siRNA) was transfected or NLRP3 inhibitor glibenclamide was added to the cell cultures. The expression of NLRP3 mRNA in HASMCs was detected by quantitative real-time PCR. The activity of caspase-1 in HASMCs was detected by colorimetric method. Results:Compared with the control group, the levels of serum creatinine and blood urea nitrogen were significantly increased in the NH model group (both P<0.01). The vascular histopathology showed that vascular intima thickened, vascular smooth muscle cells proliferated and hypertrophied, nuclei were deeply stained, and cells arranged disorderly and migrated to vascular intima in the experimental group. Quantitative analysis showed that the ratio of neointima to lumen increased significantly in the NH model group than that in control group ( P<0.01). Compared with the control group, the immunofluorescence staining of vascular tissue showed that the expressions of NLRP3, caspase-1, IL-18, IL-1β and proliferating cell nuclear antigen (PCNA) protein in the NH model group increased (all P<0.01), while the expression of α-SMA decreased ( P<0.01). NLRP3 was mainly located in vascular smooth muscle cells (VSMCs). VSMCs showed a synthetic phenotype. Compared with the NH model group, the expression of NLRP3, caspase-1, IL-18, IL-1β and PCNA protein in the NLRP3 inhibitor group and NLRP3 gene knockout group decreased (all P<0.01), the expression of α-SMA increased ( P<0.01), and the pathological changes of blood vessels alleviated. Compared with healthy serum group, the expression of NLRP3, IL-18, and IL-1β and bromodeoxyuridine (BrdU) uptake in uremic serum-stimulated group were increased (all P<0.01). After transfection of NLRP3 siRNA and addition of glibenclamide, the expression of NLRP3, IL-18, and IL-1β in VSMCs in uremic serum-stimulated group decreased, and BrdU intake decreased (all P<0.01). Conclusions:NLRP3 inflammatory bodies play an important role in promoting CKD-related neointimal hyperplasia of vessels, and glibenclamide can effectively reduce neointimal hyperplasia.

Objective To analyze mechanical characteristics for stress accumulation of the maxillary complex during expansion until complete fracture of the mid-palatal suture by using the three-dimensional (3D) finite element method, and verify validity of the model. Methods The finite element maxillary complex model containing the microimplants was established. The yield strength of the mid-palatal suture was set, and the transverse displacement of 0.25 mm was loaded every 5 ms as the load until the suture was completely fractured. The CT images of one clinical patient before and after expansion were compared and verified. Results During 0-17 ms, the stress was mainly concentrated around the microimplants, the middle of the mid-palatal suture and the zygomatico-maxillary sutures. During 18-60 ms, cracks began to occur in the mid-palatal suture, and expanded forward and backward. During 61-71 ms, the rupture path was followed by posterior part of the mid, palatal suture-the front part and the back part. Conclusions The 3D finite element model of microimplant-assisted expansion based on fracture mechanics was effective and the calculated fracture process result were more consistent with clinical practice. The research findings provide the mechanical reference model for more effective research on microimplant-assisted palatal expansion in the future.

Objective To investigate pathogenic genes related to the phenotype of fetus with severely short limbs in the first and second trimester by whole exome sequencing (WES). Methods Thirteen fetuses with severely short limbs detected by ultrasonography in the first and second trimester admitted in Chinese PLA General Hospital from September 2016 to June 2018 were collected. All cases were performed induced abortion, 6 of which were carried out karyotype analysis of amniotic fluid at the same time. WES and copy number variations (CNV) were performed on specimens from fetal tissues after labor induction. The suspected pathogenic mutations were validated by Sanger sequencing reactions. Results No abnormal karyotypes or pathological CNV were found. In 10 fetuses, pathogenic or possibly pathogenic mutations were detected in the following genes: COL2A1, FGFR3, COL1A1, COL1A2, DYNC2LI1 and TRIP11, all of which were essential to skeletal development. The diagnostic yield of WES in the fetuses with severe short limbs was 10/13. Conclusions In the first and second trimester, most of the fetuses with extremely short limbs suffer from monogenic diseases. WES is likely to be a valuable diagnostic testing option for the fetuses with severe short limbs.

Objective To explore the effect of sequential and comprehensive preventative measures on the development of premature infants' intelligence.Methods A cohort of 120 premature infants was randomly divided into an observation group and a control group,each of 60.Both groups were given routine premature infant care,but the observation group was additionally provided with sequential and comprehensive preventive intervention.It included neonatal screening,inpatient-outpatient link-up,and their parents' watching CDs explaining early childhood education and health education.All of the infants were followed up from birth to 3 years old.Their adaptive capacity,fine motor skills,language acquisition,gross motor skills and social communication were evaluated at 12,24 and 36 months old using a child intelligence developmental scale for neurological development.Development intelligence quotients (DQs) were calculated and compared.Results After 12 months,significant inter-group differences were observed in adaptability and fine motor control.At 24 and 36 months old there were also significant differences in language skills.At one,two and 3 years old the average DQ of the observation group was significantly higher than that of the control group.Significant within-group differences in average DQ were observed in both groups between 1 and 2 years old,but not between 2 and 3.Conclusion Intervention within two years after birth is critical for premature infants.Timely,sequential,integrated,preventive intervention can promote the development of intelligence and better life quality for premature infants.