OBJECTIVE To establish a management index system for off-label drug use in medical institutions， offering a reference for the improvement of the management of off-label drug use in medical institutions from Xizang region. METHODS The framework of the management index of off-label drug use was initially developed based on regulations， literature retrieval and group discussion. Then，two rounds of Delphi consultation were conducted via the “Wenjuanxing” mobile mini-program involving 10 in-hospital experts from the fields of medicine， pharmacy， and hospital management. The consultation results were then sorted， revised and statistically analyzed， the final index system was established. RESULTS The questionnaire recovery rates of the two rounds of expert consultation were both 100%. The judgment coefficients were both 0.93， the familiarity degrees were both 0.74， and the authority coefficients were 0.84 in both rounds. Kendall’s coordination coefficients were 0.278 and 0.308， respectively （P＜ 0.001）， and the full score rates in both rounds were no less than 20%. The final management index system for off-label drug use in the hospital was established， including 3 first-level indicators（off-label drug use graded management regulations， off-label drug use supervision model， off-label drug use management level quantitative assessment system）， 14 second-level indicators （such as management level classification and key points of informed consent， etc.）， and 52 third-level indicators（such as general use level， restricted-use level， and special-use level， etc.）. CONCLUSIONS The management indicators for off-label drug use developed in this study， which are established based on Delphi method， are aligned with practical needs of hospital operations and meet the standards of expert enthusiasm， authority， and consistency.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

OBJECTIVE: To investigate the differential efficacy and safety profiles of oral mucosa (OM) grafts compared with acellular dermal matrix (ADM) grafts in the surgical management of long-segment urethral strictures. METHODS: A retrospective cohort study was conducted involving 27 patients who underwent graft urethroplasty for long-segment urethral strictures in Peking University First Hospital, spanning from May 2010 to September 2023. The patient cohort comprised 14 individuals who received OM grafts and 13 who underwent ADM grafts. The participants were stratified into two groups based on the type of grafts material utilized during surgery. The demographic and clinical baseline characteristics included an average age of (43.3±14.0) years in the OM group and (54.2±15.9) years in the ADM group. The mean body mass index (BMI) for the respective groups were (24.7±4.3) kg/m² for OM and (25.4±4.8) kg/m² for ADM. Etiological differences were noted, with idiopathic causes predominantly in the OM cohort and lichen sclerosus in the ADM cohort. RESULTS: The surgical interventions were successfully executed for all the patients. The median stricture length was 4.5 (2.5, 9.0) cm for the OM group and 5.0 (2.0, 14.0) cm for the ADM group (P=0.555). The median operative duration was 160 (71, 221) min for the OM group and 134 (112, 274) min for the ADM group (P=0.065). The catheterization durations was 1.5 (1.0, 6.0) months for the OM group and 3.0 (1.0, 3.0) months for the ADM group. The median postoperative follow-up duration was 12.5 (1.0, 170.0) months for the OM group and 59.0 (3.0, 142.0) months for the ADM group. The surgical success rates were 50.00% in the OM group and 53.85% in the ADM group. No statistically significant differences were observed in postoperative quality of life (QoL) or international prostate symptom score (IPSS) at the final follow-up. The stricture-free survival rates did not differ significantly (HR=0.875, 95%CI: 0.507-1.511, P=0.6). In terms of safety, three patients in the OM group experienced sexual dysfunction, and two had oral complications, whereas the ADM group had one case of postoperative infection. CONCLUSION The findings suggest that ADM grafts are comparable to OM grafts in terms of efficacy and safety for the treatment of long-segment urethral strictures, including complex cases attributed to lichen sclerosus. However, given the small sample size of this study, the above conclusions may have certain limitations. Larger cohort studies will be needed in the future to further validate these findings.
Humans ; Urethral Stricture/surgery* ; Acellular Dermis ; Mouth Mucosa/transplantation* ; Retrospective Studies ; Middle Aged ; Male ; Adult ; Treatment Outcome ; Skin Transplantation/methods* ; Aged

Objective:To compare the aortic remodeling of the Fabulous stent system and standard thoracic aortic endovascular repair (TEVAR) on distal aorta type B aortic dissection (TBAD). Methods:The prospective data collected between Dec 2017 and Oct 2019 from 134 patients with type B aortic dissection (TBAD) who underwent treatment with the "Fabulous" stent system, and retrospective data from 159 TBAD patients receiving standard TEVAR from corresponding multicenter. By using propensity score matching analysis, we compared the prognosis and aortic remodeling outcomes in patients undergoing Fabulous and standard TEVAR treatments during a 1-year postoperative follow-up.Results:In this study, 62 patients in Fabulous group and 62 patients in standard TEVAR were included.There were no significant statistical differences in baseline characteristics between the two groups. In terms of aortic remodeling in bare stent region, Fabulous group had better change trends of diameter of true lumen [10.6 (4.4, 14.5) mm vs. 4.7 (0.9, 10.7) mm, P=0.001] and false lumen [-24.2 (-30.5, -4.9) mm vs. 0.7 (-11.8, 2.3) mm, P<0.001] than those in the standard TEVAR group. The rate of complete false lumen thrombosis was also higher in the Fabulous group (62.9% vs. 37.1%, P=0.042). Conclusion:The Fabulous stent system, when compared to standard TEVAR surgery, demonstrates good aortic remodeling outcomes in the distal aorta.

Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.

AIM: To explore the mechanism of fructus lycii in treating dry eye based on network pharmacology and experimental verification.METHODS: Taking “fructus lycii” as key words, the active ingredients and target of fructus lycii were searched by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Gene targets related to dry eye(DE)were searched by GeneCards and OMIM databases. The target genes of fructus lycii and DE were imported into Venn software to obtain the intersection target map of them. After that, the data were imported into the String database to obtain the PPI protein-protein interaction network diagram. Using Cytoscape3.7.2 software, the PPI protein-protein interaction network diagram was constructed for active ingredients, target sites and related diseases of fructus lycii. The Bioconductor platform and R language were used for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis. And the key targets in the pathogenesis of DE were verified by experiments.RESULTS: Through TCMSP, 45 types of effective chemical components of fructus lycii, 174 target genes corresponding to active components and 131 common target genes with DE were screenedout. In accordance with the network topology of “drug-composition-disease-target”, 27 main effective components of fructus lycii were found in the treatment of DE. The PPI network was analyzed according to the high degree value, which is the key targets of fructus lycii for DE treatment, mainly including AKT1, VEGFA, CASP3, IL1B, JUN, PTGS2, CXCL8, etc. According to GO enrichment analysis, 166 biological functions and processes of fructus lycii for DE treatment were obtained. KEGG enrichment analysis showed that 31 signaling pathways were involved. Additionally, experimental verification displayed that the protein expressions of AKT1, interleukin-6(IL-6), tumor necrosis factor(TNF-α)and IL-17 in conjunctiva tissue of the DE model group were significantly increased.CONCLUSIONS: Through network pharmacology, this study confirmed that the treatment of DE by fructus lycii is a complex process involving multi-components, multi-targets and multi-pathways, and that the treatment of DE by fructus lycii is mainly regulated by anti-inflammatory and apoptosis-related molecules.

Objective::To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods::This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1 st September through 31 st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group ( n = 5829) and the southern group ( n = 3246) based on the geographical division of China and male fetus group ( n = 4775) and female fetus group ( n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics. Results::A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards. Conclusion::This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.

Objective::To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods::This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1 st September through 31 st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group ( n = 5829) and the southern group ( n = 3246) based on the geographical division of China and male fetus group ( n = 4775) and female fetus group ( n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics. Results::A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards. Conclusion::This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.