Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

Objective To establishing a chromatographic analysis method for therapeutic drug monitoring of fruquintinib by high-performance liquid chromatography （HPLC）. Methods The analysis was conducted using a Welch Ultimate XB-C₁₈ （4.6 mm×150 mm, 5 μm） column with the column temperature at 35℃. The flow rate was 1.0 ml/min and the detection wavelength was at 240 nm. The mobile phase consisted of acetonitrile and 10 mmol/L potassium dihydrogen phosphate （pH 3.15）= 40∶60（V∶V）. The internal standard substance was Apatinib．All plasma samples were extracted with ethyl acetate solution. Results The linearity of Fruquintinib in plasma was good within the range of 15.63-500.00 ng/ml （r=0.999 9）. The recoveries of the method were between 95%-110% with the RSD less than 10%. The extraction rates of the method were all higher than 97%. The stability tests met the relative requirements. Conclusion A HPLC method for the determination of Fruquintinib in human plasma was established. The method had good specialty, and could be used to detect the blood concentrations of Fruquintinib in clinical practice to improve the individualized medication．

Invasive fungal disease （IFD） is a deep infectious disease with an overall increasing incidence in patients with hematologic malignancies. Triazoles， polyenes， echinocandins echinocandin antifungal drugs， 5-fluorocytosine and Compound sulfamethoxazole are the main drugs used in the clinical treatment of IFD. Therapeutic drug monitoring for IFD prevention and treatment is helpful to optimize treatment outcomes and reduce adverse effects. In this paper， the effective plasma concentration ranges of the above 5 types of drugs are systematically summarized， and the correlation between the plasma concentration of antifungal drugs and the efficacy and adverse reactions is reviewed. Solid phase extraction combined with ultra-performance chromatography-tandem mass spectrometry is a promising detection method in this research field.

OBJECTIVE To extract the effective components of Psoralea corylifolia and evaluate its efficacy in the treatment of vitiligo. METHODS The concentrations of psoralen， isopsoralen， neobavaisoflavone， corylin， psoralidin， corylifolinin， and bakuchiol in P. corylifolia extract were determined by ultra-performance liquid chromatography. Based on the analytic hierarchy process （AHP） and Plackett-Burman design， with the concentrations of the 7 components as evaluation indexes and the crushing degree， ethanol concentration， and soaking time as factors， the extraction process of P. corylifolia was optimized by Box-Behnken response surface methodology and the validation test was conducted. Zebrafish were divided into blank control group， positive control group （8-methoxypsoralen， 10.8 μg/mL）， and low-， medium-， and high-concentration groups of P. corylifolia extract （500， 1 000， 2 000 μg/mL）， with 6 fish in each group. The effects of P. corylifolia extract on the melanin production of zebrafish were studied by density analysis. RESULTS The best extraction process was P. corylifolia powder over 60 meshes and soaked in 80% ethanol for 72 hours. The average comprehensive score of three validation experiments was 98.27， with an RSD of 1.36%， and the relative error was 1.02% compared with the predicted value of the fitting equation （97.28）. Compared with the blank control group， the melanin pigmentation of zebrafish in the low-， medium-， and high-concentration groups of P. corylifolia extract was significantly increased （P＜0.01）. CONCLUSIONS The optimized extraction process of P. corylifolia is reasonable and feasible， and the obtained P. corylifolia extract can significantly promote the production of melanin in zebrafish.

OBJECTIVE：To study the effects of rat intestinal flora on the pharmacokinetic parameters of pyrazinamide and its active metabolite pyrazinoic acid. METHODS ：Totally 16 SD rats were randomly divided into trial group and control group ，with 8 rats in each group. Trial group was given mixed antibiotics （streptomycin sulfate+neomycin sulfate ）intragastrically to construct pseudoaseptic rat model. After modeling ，both groups were given pyrazinamide intragastrically （150 mg/kg）. Before and 0.167， 0.333，0.667，1，1.5，2，3，4，6，9 h after administration ，0.1 mL blood sample was collected from orbital venous plexus ，and 0.3 mL blood sample was collected from orbital venous plexus 12，24 h after administration. Using phenacetin as internal standard ， LC-MS/MS method was adopted to determine the plasma concentration of pyrazinamide and pyrazinoic acid. The determination was performed on Agilent ZORBAX SB-Aq column with mobile phase consisted of 0.2％ formic acid （containing 8 mmol/L ammonium acetate）-methanol（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 30 ℃，and sample size was 10 μL. The ion source was ESI and the temperature of ion source was 500 ℃. The collision gas was nitrogen and the pressure was 10 psi. The temperature of mass transfer interface was 100 ℃. The mass spectrum monitoring mode was multi reaction monitoring ， and the collection mode was positive ion mode. The monitoring transition ion-pairs were m/z 124.0→79.0（pyrazinamide），m/z 125.1→79.1（pyrazinic acid ）and m/z 180.0→110.2（internal standard ）. The de-clustering potential and collision voltage were 55， 26 and 85 V，24，23 and 28 V，respectively. The pharmacokinetic parameters were calculated and compared by using DAS 2.1.1 software. RESULTS ：The linear ranges of pyrazinamide and pyrazinoic acid were 25-5 000 ng/mL（r＝0.997 6）and 100-12 500 ng/mL（r＝0.999 0）. The lower limits of quantification were 25 and 100 ng/mL，respectively. Intra-batch and inter-batch accuracy were 92.93％-100.50％，and RSDs of intra-batch and inter-batch precision and matrix effect tests were all lower than or equal to 8.42％（n＝6 or n＝3）. Compared with control group ，tmax of pyrazinamide in trial group was prolonged significantly （P＜0.01）； there was no statistical significance in other pharmacokinetic parameters between 2 groups（P＞0.05）. CONCLUSIONS ：The absorption of single dose pyrazinamide is delayed with the change of intestinal flora in rats.

Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs. Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP₁₈ column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside. Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, c_max was (9 680±3725) and (9 310±1 645) ng/ml; t_max was (1.25±0.67) and (0.011±0.017) h, AUC_0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC_0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t_1/2 was (1.31±0.63) and (0.98±0.13) h, respectively. Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%.

OBJECTIVE：To analyze the mass spectrometry fragmentation regularity of bicyclol ，bifendate and schisandrin C ， and to identify the impurities of bicyclol raw material. METHODS ：UHPLC-ESI-Q-TOF-MS method was adopted. Using electrospray ionization source ，in positive ion mode ，the excimer ion and characteristic fragments of bicyclol ，bifendate and schisandrin C were analyzed by means of TOF-MS. According to the mass change of fragments ，the possible fragmentation pathways were speculated ，and the fragmentation regularity were analyzed and summarized. Bicyclol raw material sample was first separated by liquid chromatography to find the impurity peaks in it ，and then the impurity peaks were analyzed by mass spectrometer；the impurity identification was conducted by combining with the fragmentation regularity. RESULTS ：The 3 compounds all produced [M+H] + excimer ion in the positive ion mode. After collision-induced dissociation ，the C-O bond ，the simple rupture of the C-C bond and the ring-opening cleavage of the oxygen ring occurred ；with the loss of neutral fragments ， mainly CH 2O，supplemented by CO 2，CO and CHO ，the dissociation was concentrated in the middle and high quality regions. C-C and C-O bonds of 3 compounds were simply broken only in the branched chain structure and/or oxygen ring structure ，but the structure of the biphenyl parent nucleus remained unchanged. Among them ，the bicyclol contained a benzyl alcohol structure ，so under acidic mobile phase conditions ，it would exist stably in the form of [M+H －H2O]+. Because schisandrin C contained 8-membered ring structure，ring opening first occurred under collision voltage ，and then neutral fragment loss occurred. The secondary mass spectra of impurity in bicyclol raw material were consistent with the mass spectra fragmentation of secondary fragments of bifendate. CONCLUSIONS：The study summarized mass spectrometry fragmentation regularity of 3 schisandrin derivatives. The impurity in bicyclol raw material may be bifendate.

OBJECTIVE：To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS ：The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ，LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3，respectively. RESULTS ： Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL（R2＞0.996 7）. The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12％ （n＝6 or n＝3）. Accuracies were 90.92％-108.00％（n＝6 or n＝3）. The average extraction recoveries were 87.51％-100.00％（RSD＜8％，n＝6）. The average matrix effects were 96.66％-99.93％（RSD＜5％，n＝6）. The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS ：The method is simple ，accurate and specific ，and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.

Objective:To explore the application effect of nursing intervention based on the trans-theoretical model (TTM) in pelvic floor muscle training (PFMT) of patients with postpartum urinary incontinence.Methods:Using the convenient sampling method, a total of 128 patients with postpartum urinary incontinence who were treated at the Pelvic Floor Rehabilitation Center of Peking Union Medical College Hospital from August 2019 to August 2020 were selected as the research objects. The patients were grouped according to the time of their visits. A total of 64 patients admitted from August to December 2019 were set as the control group and the 64 patients admitted from January to August 2020 were set as the observation group. The control group received routine nursing and health guidance and the observation group received nursing intervention based on the trans-theoretical model on this basis. Before intervention and 12 weeks after intervention, patients in the two groups were evaluated for urine leakage volume in 1-hour pad test, compliance of pelvic floor muscle training and the stage of behavior change.Results:After 12 weeks of intervention, the compliance of the observation group was better than that of the control group, and the difference was statistically significant ( P<0.01) . After 12 weeks of intervention, the urine leakage volume in 1-hour pad test in observation group was less than that in the control group, and the difference was statistically significant ( P<0.01) . After 12 weeks of intervention, the number of patients in the action stage and maintenance stage in the observation group was higher than that in the control group, and the difference was statistically significant ( P<0.01) . Conclusions:The application of nursing intervention based on the trans-theoretical model can improve the compliance and treatment effect of pelvic floor muscle training in patients with postpartum urinary incontinence and promote the establishment of healthy behaviors.

Objective: To report the effects of operative treatment of Sneppen Ⅴ talus fracture through the approach for malleolus medialis Ⅴ osteotomy plus hollow compression screw fixation. Methods: From January 2015 to January 2019, 16 patients with Sneppen Ⅴ talus fracture were treated at Department Ⅱ of Hand & Foot Microsurgery, The Second Affiliated Hospital to Inner Mongolia Medical University. They were 14 men and 2 women with a mean age of 38.4 years (range, from 20 to 55 years). All fractures were fixed with hollow compression screws through the approach for malleolus medialis Ⅴ osteotomy. The ankle and hindfoot functional scoring system developed by American Orthopaedic Foot and Ankle Society (AOFAS) was used to evaluate the clinical outcomes. Results: All patients were followed up for a mean time of 12.6 months (range, from 6 to 30 months). The mean operation time was 68.4 minutes (range, from 52 to 96 minutes); the mean amount of hemorrhage during operation was 96.8 mL (range, from 48 to 122 mL); the mean period of bone union was 4.8 months (range, from 3 to 8 months). The postoperative mean AOFAS score was 75.3 points (range, from 43 to 91 points). Complications occurred in 4 cases, including one case of talus ischemic necrosis, one case of partial talus ischemic necrosis accompanied by tibial arthritis, one case of subtalar arthritis, and one case of combined tibial, talar and subtalar arthritis. All incisions obtained primary healing, with no complications like infection, screw breakage, delayed union or nonunion. Conclusion Operative treatment of Sneppen Ⅴ talus fracture through the approach for malleolus medialis Ⅴ osteotomy plus hollow compression screw fixation can provide sufficient operative exposure to facilitate reduction and fixation of the talus fracture so that the ischemic necrosis of the talus and traumatic arthritis can be effectively reduced.