OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Objective To investigate the effect of miR-199a-5p on common bile duct ligation(BDL)-induced liver fibrosis in rats by regulating intestinal flora.Methods The 25 SD rats were randomly divided into five groups:the Sham group,the BDL group,the negative control adenovirus(NC adv)group,the miR-199a-5p adv group and the miR-199a-5p sponge adv group.The pathological changes of liver tissue and the degree of liver fibrosis were ob-served by HE,Masson and Sirius Red staining.The levels of aspartate aminotransferase(AST),alanine amin-otransferase(ALT),total bilirubin(TBIL)and direct bilirubin(DBIL)in serum of rats were determined by a fully automatic biochemical analyzer.The mRNA expression level of miR-199a-5p in liver tissue of rats was detec-ted by qRT-PCR.The protein expression levels of α-smooth muscle actin(α-SMA)and collagen type 1 alpha 1(COL1A1)in liver tissue of rats were detected by double immunofluorescence staining and Western blot experi-ment.Rat feces were collected for 16S rRNA high-throughput sequencing.Results The expression of miR-199a-5p was up-regulated in the liver tissue of BDL rats(P＜0.01).Compared with the NC adv group,the degree of liver injury and collagen deposition were relatively serious,the levels of AST,ALT,TBIL and DBIL in serum and the expression levels of α-SMA and COL1A1 in liver tissue increased in the miR-199a-5p adv group(all P＜0.05).However,the results of miR-199a-5p sponge adv intervention were opposite(all P＜0.05).The 16S rRNA sequencing results showed that rats treated with miR-199a-5p adv were characterized by increased diversity and richness of intestinal microbiota,changed composition of intestinal microbiota,while the results of miR-199a-5p sponge adv interfering with the bacterial community were opposite(all P＜0.05).Conclusion miR-199a-5p promotes liver fibrosis of BDL rats,and its mechanism may be related to regulating the diversity and abundance of intestinal microbiota.

Objective:To explore the application effect of theory of inventive problem solving(TRIZ)in the management of loaner instruments in central sterile supply department(CSSD).Methods:TRIZ management team was set up to analyze problems in cleaning,disinfection and sterilization of loaner instruments.The invention principles of TRIZ were compared to determine targeted solutions to the corresponding problems.A total of 1,000 pieces of loaner instruments received by The Third Affiliated Hospital of Air Force Medical University were selected from January and December 2023 were selected,the 500 pieces received from January to June were managed by routine standard management mode,and the 500 pieces received from July to December were managed by the TRIZ management mode.The qualification rates of instruments cleaning,disinfection,packaging and sterilization,the incidence of adverse events,the satisfaction scores of clinical departments and assessment results of newly hired nurses of CSSD were compared between the two management modes.Results:The qualification rates of instruments cleaning,disinfection,packaging and sterilization of TRIZ management mode were 98.00%(490/500),97.20%(486/500),96.40%(482/500)and 96.00%(480/500),respectively,which were higher than those of routine standard management mode,the difference was statistically significant(x2=12.029,11.685,8.859,8.322,P<0.05).The incidence of adverse events of TRIZ management mode was 0%,the routine standard management mode was 1.20%,the difference was statistically significant(x2=6.036,P<0.05).The average scores of CSSD newly hired nurses in of theoretical knowledge,treatment process,cleaning,disinfection and sterilization and packaging of TRIZ management mode were(89.20±6.69)points,(88.47±3.48)points,(92.47±5.37)points and(92.00±5.83)points,respectively,which were higher than those of routine standard management mode,the difference was statistically significant(t=3.993,4.402,3.926,3.332,P<0.05).The satisfaction scores of clinical department personnel with instruments quality,distribution,handover,information traceability,service attitude and overall satisfaction of TRIZ management mode were(18.65±0.81)points,(18.85±1.04)points,(18.95±1.05)points,(18.40±0.75)points,(18.35±0.93)points and(93.20±1.91)points,respectively,which were higher than those of the routine standard management mode,the difference was statistically significant(t=3.599,5.889,4.851,4.865,2.075,8.723,P<0.05).Conclusion:The application of TRIZ in the management of loaner instruments in CSSD can significantly improve theoretical knowledge and practical skills of newly hired nurses in CSSD,thereby improving the qualification rates of instruments cleaning,disinfection,packaging and sterilization of loaner instruments,reducing the occurrence of instrument-related adverse events and improving satisfaction of department personnel with instruments use.

Objective To explore the changes in periretinal defocus and visual quality after femtosecond laser-assis-ted in situ keratomileusis(FS-LASIK).Methods Fifty-one myopic patients(102 eyes)who underwent FS-LASIK at the Ineye Hospital of Chengdu University of Traditional Chinese Medicine from March to May 2023 were selected for the study,including 27 females(54 eyes)and 24 males(48 eyes).The defocus around the retina was measured using a multispectral refraction topography,and the total refraction difference value(TRDV)was recorded.The refraction difference value(RDV)in four quadrants:superior RDV(RDV-S),inferior RDV(RDV-I),nasal RDV(RDV-N),and temporal RDV(RDV-T),as well as the RDV in the concentric ring areas corresponding to 10°,20°,30°,40°,and 53° from the fovea of the mac-ula(represented as RDV 0°-10°,RDV 10°-20°,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53°,respectively)were also re-corded.The objective scattering index(OSI),Strehls ratio(SR),modulation transfer function(MTF)values(represen-ted as 10 c·d-1 MTF,20 c·d-1 MTF,and 30 c·d-1MTF,respectively)and cutoff frequencies(MTF cutoff)at the spa-tial frequencies of 10 c·d-1,20 c·d-1 and 30 c·d-1 were measured and recorded using a visual quality analysis system.The data of corneal vertical trefoil(Z3-3),vertical coma(Z3-1),horizontal coma(Z31),horizontal trefoil(Z33),vertical tetrafoil(Z4-4),vertical secondary astigmatism(Z4-2),spherical aberration(Z40),horizontal secondary astigmatism(Z42),horizontal tetrafoil(Z44),and total higher-order aberration(HOA)were measured and recorded using the iTrace aberration meter.The measurement data of patients before surgery,one month after surgery,and three months after sur-gery were compared,and their correlations were analyzed.Results TRDV,RDV-S,RDV-N,RDV 20°-30°,RDV 30°-40°,and RDV 40°-53° around the retina of patients decreased one month and three months after surgery compared with those be-fore surgery,and the differences were statistically significant(all P＜0.001).There were statistically significant differences in OSI,MTF cutoff,and 10 c·d-1 MTF among patients before surgery,one month after surgery,and three months after surgery(all P＜0.05).There were statistically significant differences in corneal Z3-3,Z3-1,Z31,Z33,Z4-4,Z4-2,Z40,Z42,Z44,and HOA among patients before surgery,one month after surgery,and three months after surgery(all P＜0.001).The Pearson correlation analysis results showed that,ΔRDV 0°-10° was positively correlated with ΔZ3-3,ΔZ31,ΔZ4-2,ΔZ40,and ΔZ42(all P＜0.05);ΔRDV 10°-20° was positively correlated with ΔZ4-4 and ΔZ4-2(both P＜0.05);ΔRDV 20°-30° was positively correlated with ΔZ4-4 and ΔZ44(both P＜0.05);ΔTRDV and ΔRDV 40°-53° were negatively correla-ted with ΔHOA(both P＜0.05).ΔRDV-S and ΔZ3-1 were negatively correlated with ΔHOA(both P＜0.05)and positively correlated with ΔZ44(P＜0.05);ΔRDV-N was positively correlated with ΔZ4-4(P＜0.05).Conclusion FS-LASIK can reduce periretinal hyperopic defocus in myopic patients,but it introduces corneal HOA,and there is a certain correlation between the two.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective:To investigate the current situation of occurrence of social isolation in maintenance hemodialysis patients and analyze its influencing factors, in order to provide a theoretical basis for the implementation of targeted interventions.Methods:The study was a cross-sectional study. A total of 315 dialysis patients in three hemodialysis centers in Xinjiang were selected by simple sampling method from October 2021 to March 2022, who were investigated using the general information questionnaire, Lubben-6 social network scale, International Physical Activity Questionnaire (sedentary behavior section), Patient Health Questionnaire 9-item scale (PHQ-9) and Frail Scale. Univariate analysis and binary Logistic regression analysis were used to explore the influencing factors affecting the social isolation of dialysis patients.Results:Social isolation was present in 28.89% (91/315) of maintenance hemodialysis patients, and binary Logistic regression analysis revealed that age (45-59 years old: OR=4.815, 95% CI 1.362-17.017;≥60 years old: OR=8.968, 95% CI 2.349-34.236), dialysis age ( OR=2.788, 95% CI 1.334-5.826), sedentary behavior ( OR=2.504, 95% CI 1.406-4.461), depression ( OR=2.095, 95% CI 1.179-3.722), and debilitation ( OR=2.043, 95% CI=1.062-3.933) were influencing factors of social isolation in maintenance hemodialysis patients (all P<0.05). Conclusions:The occurrence of social isolation in maintenance hemodialysis patients was closely associated with advanced age, high dialysis age, sedentary behavior, debilitation, and depressive status, suggesting that medical staff in hemodialysis centers can implement targeted interventions to prevent or improve the level of social isolation in patients based on relevant influencing factors.

Objective:To analyze the clinical characteristics of benign paroxysmal positional vertigo (BPPV) in the oldest old.Method:The clinical data of elderly patients (≥60 years old) with BPPV diagnosed in the Clinical Center for Vertigo and Balance Disturbance of Capital Medical University between January 2019 and October 2021 was collected, including basic information, clinical symptoms in a structured medical history questionnaire and the time interval from the appearance of symptoms to medical consultation. According to the age, patients were divided into elderly group (60-74 years old) and the oldest old group (≥75 years old), and the demographic information, clinical symptoms and consultation time were compared between the two groups.Results:A total of 3 019 patients with BPPV were included in analysis; there were 415 patients in the oldest-old group with the age of (79.54±3.62) years, and 2 604 patients in the elderly group with the age of (65.59±3.88) years. The incidence of vertigo, dizziness or vertigo triggered by position changes of head or body, headache and autonomic symptoms in the eldest-old group were less common than that in the elderly group (all P<0.05). But hearing loss and other types of dizziness (unable to determine the nature of dizziness or vertigo, or without typical symptoms such as dizziness, balance disorders, or instability) were more common in the eldest-old group than those in the elderly group (all P<0.05). Among 3 019 patients, 1 137 had definite time from symptom onset to diagnosis (1 004 in the elderly group and 133 in the oldest-old group), the proportion of patients with the time from the onset to diagnosis>7 days in the oldest-old group was higher than that in the elderly group ( P<0.05). Conclusion:The oldest old patients with BPPV have more atypical symptoms than the younger elderly patients.

Objective:To investigate the functional imaging parameters that effectively distinguish isocitrate dehydrogenase (IDH) gene mutation status in clinical practice with long echo time (TE) point-resolved spectroscopy (PRESS) MRS.Methods:Totally 25 patients with suspected diagnosis of low grade gliomas(LGGs; Grade II) were recruited prospectively and divided into IDH mutation group and IDH wild group according to pathological results in the study. All patients were scanned with long TE PRESS MRS. In addition, IDH mutational status was determined by post-operation Sanger sequencing. The t test or Mann-Whitney U test was used to analyze the differences of 2-hydroxyglutarate (2HG), Glutamate (Glu), Glutamine (Gln) and 2HG/Glu+Gln between the IDH mutation group and the IDH wild group, then ROC curve was plotted with statistically significant indexes to obtain the efficacy of predicting IDH mutation status. Results:Of the 25 patients, 19 had IDH mutant gliomas and 6 had IDH wild-type gliomas. 2HG, Glu, Gln and 2HG/Glu+Gln in IDH mutated group were 1.42 (1.09, 1.93)mmol/L, (1.74±1.31)mmol/L, (1.68±0.66)mmol/L, 0.55 (0.28, 0.77), respectively; while the corresponding values were 0.00 (0.00, 1.30)mmol/L, (3.28±1.02)mmol/L, (2.55±1.47)mmol/L, 0.00 (0.00, 0.26) in IDH gene wild type group, respectively. The differences of 2HG, Glu, and 2HG/Glu+Gln between the two groups were statistically significant ( P values were 0.030, 0.016, 0.004, respectively). The area under the ROC curve of 2HG/Glu+Gln was the largest (0.877), and the sensitivity was the highest (84.2%). Conclusion:The integration of 2HG with Glu and Gln can effectively realize the noninvasive assessment of IDH mutation status.