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 explore the efficacy of atezolizumab combined with anlotinib in treating advanced non-small cell lung cancer (NSCLC) .Methods:A total of 80 patients with advanced NSCLC treated in the Baoding No.2 Central Hospital from September 2019 to September 2023 after second-line treatment were selected as research subjects. Patients who received only anlotinib treatment were included in the monotherapy group ( n=40), while patients who received atezolizumab combined with anlotinib treatment were included in the combination group ( n=40). The clinical efficacy and serum levels of carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) of the two groups were compared. Kaplan-Meier survival curve was used to analyze the survival of the two groups. The functional assessment of cancer therapy-lung cancer (FACT-L) was used to assess the quality of life of patients in both groups before and after treatment. The incidence of adverse reactions was compared between the two groups. Results:After four cycles of treatment, the objective response rate (ORR) of the combination group was 37.50% (15/40), which was higher than that of the monotherapy group [17.50% (7/40) ], with a statistically significant difference ( χ2=4.01, P=0.045). The disease control rates (DCRs) of the two groups were 85.00% (34/40) and 75.00% (30/40), respectively, with no statistically significant difference ( χ2=1.25, P=0.264). Before treatment, the CEA levels in combination group and monotherapy group were (10.18±2.15) and (10.14±2.02) μg/L, and the VEGF levels were (804.04±46.58) and (809.10±43.63) ng/L, respectively, with no statistically significant difference (both P>0.05). After treatment, the serum CEA levels of patients in combination group and monotherapy group were (4.35±1.05) and (6.63±1.37) μg/L, and the VEGF levels were (431.26±50.19) and (549.92±55.27) ng/L, respectively, with statistically significant differences ( t=8.35, P<0.001; t=10.05, P<0.001), and the levels of serum CEA and VEGF in the two groups after treatment were lower than before treatment ( t=32.47, P<0.001; t=21.73, P<0.001; t=88.65, P<0.001; t=58.27, P<0.001). Survival analysis showed that the median progression-free survival (PFS) of the monotherapy group and the combination group were 4.12 and 6.06 months, respectively, with a statistically significant difference ( χ2=17.70, P<0.001), the median overall survival (OS) were 11.8 and 12.7 months, respectively, with no statistically significant difference ( χ2=3.09, P=0.079). Before treatment, the FACT-L scores of patients in combination group and monotherapy group were 61.20±6.98 and 60.52±7.14, respectively, with no statistically significant difference ( t=0.43, P=0.668). After treatment, the FACT-L scores of the two groups were 83.24±9.38 and 74.58±7.86, respectively, with a statistically significant difference ( t=4.48, P<0.001), and the FACT-L scores of the two groups after treatment were all higher than before treatment ( t=29.36, P<0.001; t=21.51, P<0.001). During treatment, the total incidence of drug-related adverse reactions in two groups was 42.50% (17/40) and 55.00% (22/40), respectively, with no statistically significant difference ( χ2=1.25, P=0.263) . Conclusions:Atezolizumab combined with anlotinib in the treatment of advanced NSCLC can enhance the short-term efficacy, prolong the PFS of patients, improve the quality of life, and the related adverse reactions are tolerable.

Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.

Objective:To investigate the effectiveness and feasibility of a 3D U-Net in conjunction with a three-phase CT image segmentation model in the automatic segmentation of GTVnx and GTVnd in nasopharyngeal carcinoma.Methods:A total of 645 sets of computed tomography (CT) images were retrospectively collected from 215 nasopharyngeal carcinoma cases, including three phases: plain scan (CT), contrast-enhanced CT (CTC), and delayed CT (CTD). The dataset was grouped into a training set consisting of 172 cases and a test set comprising 43 cases using the random number table method. Meanwhile, six experimental groups, A1, A2, A3, A4, B1, and B2, were established. Among them, the former four groups used only CT, only CTC, only CTD, and all three phases, respectively. The B1 and B2 groups used phase fine-tuning CTC models. The Dice similarity coefficient (DSC) and 95% Hausdorff distance (HD95) served as quantitative evaluation indicators.Results:Compared to only monophasic CT (group A1/A2/A3), triphasic CT (group A4) yielded better result in the automatic segmentation of GTVnd (DSC: 0.67 vs. 0.61, 0.64, 0.64; t = 7.48, 3.27, 4.84, P < 0.01; HD95: 36.45 vs. 79.23, 59.55, 65.17; t = 5.24, 2.99, 3.89, P < 0.01), with statistically significant differences ( P < 0.01). However, triphasic CT (group A4) showed no significant enhancement in the automatic segmentation of GTVnx compared to monophasic CT (group A1/A2/A3) (DSC: 0.73 vs. 0.74, 0.74, 0.73; HD95: 14.17 mm vs. 8.06, 8.11, 8.10 mm), with no statistically significant difference ( P > 0.05). For the automatic segmentation of GTVnd, group B1/B2 showed higher automatic segmentation accuracy compared to group A1 (DSC: 0.63, 0.63 vs. 0.61, t = 4.10, 3.03, P<0.01; HD95: 58.11, 50.31 mm vs. 79.23 mm, t = 2.75, 3.10, P < 0.01). Conclusions:Triphasic CT scanning can improve the automatic segmentation of the GTVnd in nasopharyngeal carcinoma. Additionally, phase fine-tuning models can enhance the automatic segmentation accuracy of the GTVnd on plain CT images.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells,plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province,explore the distribution of monitoring values and the change of monitoring level,so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei.Methods In 2023,the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected,scatter plots were made and the range markers were set,and the"mean±SD"line was taken as the upper limit and lower limit of the measurement range.In 2024,the monitoring values in 2023 were added,and the changes of two measurement ranges were compared to analyze the stability and overall level.Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin,washed erythrocyte-hemoglobin,washed erythrocyte-su-pernatant protein,cryoprecipitate coagulation factor-FⅧ,fresh frozen plasma-FⅧ,leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993,6.252 to 6.104,0.273 to 0.267,57.506 to 56.276,0.920 to 0.892,0.653 to 0.644 and 2.653 to 2.603,respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced disper-sion.Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells,hemoglobin content of the wash eryth-rocyte,protein content of supernatant of the wash erythrocyte,hemolysis rate of the wash erythrocyte,FⅧ content of the cryoprecipitate coagulation factor,plasma protein content of the fresh frozen plasma,FⅧ content of the fresh frozen plasma,platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476,44.915 to 44.861,0.280 to 0.283,0.137 to 0.142,133.989 to 133.271,60.262 to 60.208,1.301 to 1.277 and 3.036 to 3.033,respectively,and was closer to the national standard line,which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023.The long-term qualified rate of coagulation items was low,and no improvement has been ob-served.The stability of biochemical items has been enhanced but overall deviation has occurred,with the average value close to the national standard line.The possibility of subsequent testing failure has increased.The counting items showed no obvi-ous common characteristics.Conclusion The use of"mean±SD"in the analysis can visually display the distribution of mo-nitoring values of different items in Hebei,forming an indicator measurement range covering the past nine years.It shows the characteristics of each item,and provides reference for subsequent quality control laboratory data analysis of each blood sta-tions to takes active measures to improve the monitoring level.

OBJECTIVE To observe the clinical efficacy and effect on serum thymic stromal lymphopoietin(TSLP)levels of pa-tients with advanced liver cancer of qi deficiency and toxic stasis type by Jiawei Yupingfeng San.METHODS Using random double blind method,120 patients with advanced liver cancer of qi deficiency and toxic stasis type were randomly divided into 3 groups:Jiawei Yupingfeng San group,Yupingfeng San group,and placebo group,each consisting of 40 cases.All patients in the 3 groups were given conventional treatment such as radiotherapy,chemotherapy,interventional or targeted therapy;Jiawei Yupingfeng San group was given Jiawei Yupingfeng San granules,Yupingfeng San group was given Yupingfeng San granules,and placebo group was given placebo.The course of treatment was 2 months.The changes of Karnofsky functional status score(KPS score),TCM syndrome score,tumor size and serum TSLP level in the 3 groups were observed before and after treatment,and the correlation between the changes of tumor size and TSLP was analyzed.RESULTS After treatment,the KPS scores of Yupingfeng San group and Jiawei Yupingfeng San group were sig-nificantly increased(P<0.05,P<0.01),TCM syndrome score were decreased(P<0.01),tumor growth(P<0.05,P<0.01)was de-layed,and serum TSLP levels(P<0.05,P<0.01)were decreased.Furthermore,there was a slight positive correlation between chan-ges in tumor size and changes in TSLP(P<0.05).In terms of improving tumor size,the curative effect of Jiawei Yupingfeng San group was better than that of Yupingfeng San group(P<0.05).During the treatment period,no obvious adverse reactions were observed in the 3 groups of patients.CONCLUSION Combined with conventional treatment,Jiawei Yupingfeng San can significantly delay tumor growth in patients with advanced liver cancer of qi deficiency and toxic stasis type and improve patients'TCM syndromes and their qual-ity of survival.The therapeutic mechanism is related to reducing the expression of serum TSLP and improving the immune status of pa-tients,thereby delaying the growth of tumors.

Objective:To investigate the clinical characteristics and survival prognosis of patients with triple/quad-class exposed relapsed or refractory multiple myeloma(RRMM).Methods:The clinical data of patients with triple/quad-class exposed RRMM from eight centers in Shanxi Province between May 2017 and May 2024 were retrospectively analyzed.Overall survival(OS)and progression-free survival(PFS)were analyzed using the Kaplan-Meier method,and factors affecting survival were examined by the Cox proportional hazards model and Log-rank test.Results:Among the 112 patients with triple-class exposure,16 were quadruple-class exposed.The detection rates of high-risk cytogenetic abnormalities and extramedullary lesions in patients with triple-class exposure were 57.1%and 36.6%,respectively,while those in patients with quadruple-class exposure were 87.5%and 62.5%,respectively.The median PFS and OS of patients with triple-class expos-ure were 5.6 months and 12.2 months,respectively,while those of patients with quadruple-class exposure were 9.4 months and 16.9 months,respectively.Cox model analysis showed that extramedullary lesions and multi-line treatment(≥3 lines)were independent risk factors for the survival of patients with triple-class exposed RRMM(P<0.05).Previous autologous stem cell transplantation,subsequent con-ventional drug treatment,and B-cell maturation antigen(BCMA)chimeric antigen receptor T-cell(CAR-T)treatment were protective factors(P<0.05).After triple-class drug resistance,the Log-rank test verified that BCMA CAR-T treatment significantly prolonged the median PFS of patients compared to conventional drug treatment(9.4 months vs.5.2 months,P=0.026 9),whereas the difference in OS was not statistic-ally significant(16.9 months vs.7.9 months,P=0.263 4).Conclusions:Patients with triple/quad-class exposed RRMM have a poor prognosis,and BCMA CAR-T cell therapy can improve survival in patients with triple-class drug-resistant RRMM.

Objective:To investigate the clinical characteristics and survival prognosis of patients with triple/quad-class exposed relapsed or refractory multiple myeloma(RRMM).Methods:The clinical data of patients with triple/quad-class exposed RRMM from eight centers in Shanxi Province between May 2017 and May 2024 were retrospectively analyzed.Overall survival(OS)and progression-free survival(PFS)were analyzed using the Kaplan-Meier method,and factors affecting survival were examined by the Cox proportional hazards model and Log-rank test.Results:Among the 112 patients with triple-class exposure,16 were quadruple-class exposed.The detection rates of high-risk cytogenetic abnormalities and extramedullary lesions in patients with triple-class exposure were 57.1%and 36.6%,respectively,while those in patients with quadruple-class exposure were 87.5%and 62.5%,respectively.The median PFS and OS of patients with triple-class expos-ure were 5.6 months and 12.2 months,respectively,while those of patients with quadruple-class exposure were 9.4 months and 16.9 months,respectively.Cox model analysis showed that extramedullary lesions and multi-line treatment(≥3 lines)were independent risk factors for the survival of patients with triple-class exposed RRMM(P<0.05).Previous autologous stem cell transplantation,subsequent con-ventional drug treatment,and B-cell maturation antigen(BCMA)chimeric antigen receptor T-cell(CAR-T)treatment were protective factors(P<0.05).After triple-class drug resistance,the Log-rank test verified that BCMA CAR-T treatment significantly prolonged the median PFS of patients compared to conventional drug treatment(9.4 months vs.5.2 months,P=0.026 9),whereas the difference in OS was not statistic-ally significant(16.9 months vs.7.9 months,P=0.263 4).Conclusions:Patients with triple/quad-class exposed RRMM have a poor prognosis,and BCMA CAR-T cell therapy can improve survival in patients with triple-class drug-resistant RRMM.

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)%.

Adult ; Antibodies, Viral/isolation & purification* ; COVID-19/virology* ; Feces/chemistry* ; Female ; Humans ; Intestines/virology* ; Male ; RNA, Ribosomal, 16S/genetics* ; RNA, Viral/isolation & purification* ; SARS-CoV-2/pathogenicity*