Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

Purpose: This study aimed to evaluate and optimize microbial DNA extraction methods from urine, a non-invasive sample source, to enhance DNA quality, purity, and reliability for urinary microbiome research and biomarker discovery in bladder cancer. Materials and Methods: A total of 302 individuals (258 with genitourinary cancers and 44 with benign urologic diseases) participated in this study. Urine samples were collected via sterile catheterization, resulting in 445 vials for microbial analysis. DNA extraction was performed using three protocols: the standard protocol (SP), water dilution protocol (WDP), and chelation-assisted protocol (CAP). DNA quality (concentration, purity, and contamination levels) was assessed using NanoDrop spectrophotometry.Microbial analysis was conducted on 138 samples (108 cancerous and 30 benign) using 16S rRNA sequencing. Prior to sequencing on the Illumina MiSeq platform, Victor 3 fluorometry was used for validation. Results: WDP outperformed other methods, achieving significantly higher 260/280 and 260/230 ratios, indicating superior DNA purity and reduced contamination, while maintaining reliable DNA yields. CAP was excluded due to poor performance across all metrics. Microbial abundance was significantly higher in WDP-extracted samples (p<0.0001), whereas SP demonstrated higher alpha diversity indices (p<0.01), likely due to improved detection of low-abundance taxa. Beta diversity analysis showed no significant compositional differences between SP and WDP (p=1.0), supporting the reliability of WDP for microbiome research. Conclusions WDP is a highly effective and reliable method for microbial DNA extraction from urine, ensuring high-quality and reproducible results. Future research should address sample variability and crystal precipitation to further refine microbiome-based diagnostics and therapeutics.

Objective To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures.Methods A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021.Among them,37 patients were treated with F screw internal fixa-tion,including 16 males and 21 females,aged47 to 64years old with an average of(53.87±5.28)years old;According to Pauwels classification,there were 1 case of type Ⅰ,19 cases of type Ⅱ,17 cases of type Ⅲ;8 cases of combined medical diseases;17 cases of falling,8 cases of traffic accident and 12 cases of falling from height;The time from injury to operation was 29 to 49 hours with average of(35.00±7.34)hours.Another 35 cases used internal fixation with an inverted triangle parallel nail,including 13 males and 22 females with an average age of 46 to 63 years old(52.36±5.05)years old;According to the Pauwels injury classifi-cation:there were 2 cases of type Ⅰ,21 cases of type Ⅱ,12 cases of type Ⅲ;6 cases of medical diseases,15 cases of falling in-jury,9 cases of traffic accident,11 cases of falling injury;The time from injury to operation was 30 to 45 hours with an average of(33.00±6.83)h.The intraoperative blood loss,operation time,intraoperative fluoroscopy times,follow-up time,fracture healing time,postoperative complications were observed and compared between the two groups.The hip joint function was e-valuated by Harris score at 6 months and 12 months after operation.Results There was no significant difference in operation time,intraoperative blood loss,intraoperative fluoroscopy times and other intraoperative data between two groups(P＞0.05).Both groups were followed up regularly,and the follow-up time was 12 to 16 months.The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group(P＜0.05).There was 1 case of femoral neck shortening in the F screw internal fixation group,1 case of nonunion,1 case of nail withdrawal,and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group.The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group(P＜0.05).Conclusion Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures.It can significantly shorten the fracture healing time,reduce the incidence of postoperative complications,significantly improve hip joint function,and improve the quality of life.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

To improve the current situation of multiple preoperative visits and evaluations for elderly patients and other patients with complex conditions, in December 2022, Peking Union Medical College Hospital established preoperative multidisciplinary evaluation clinic (shorted as joint clinic). The joint clinic established a multidisciplinary team, clarified service targets, and developed standardized clinic workflows to provide patients with a " one-stop" preoperative assessment(physical fitness assessment, nutritional assessment, and frailty assessment, etc.), nutritional optimization intervention, and prerehabilitation education and guidance services. This practice strengthened preoperative risk management, improved preoperative assessment efficiency, and ensured the safety of patients during the perioperative period. As of September 2023, the joint clinic had received a total of 128 patients, of which 86 underwent surgery after preoperative evaluation and prehabilitation optimization. The obesity rate, smoking rate, and number of frailty cases of these patients had decreased from 13.96%, 11.63%, and 18 at the time of visit to 9.30%, 4.65%, and 14 on the day before surgery, respectively. They had recovered well after surgery. This practice had improved the preoperative status of patients and created conditions for high-risk patients to undergo surgery smoothly, so as to provide references for other hospitals to carry out multidisciplinary collaborative preoperative evaluation works.

Purpose: T1 high grade (T1HG) bladder cancer (BC) is a type of non-muscle invasive BC (NMIBC) that is recognized as an aggressive subtype with a heightened propensity for progression. Current risk stratification methods for NMIBC rely on clinicopathological indicators; however, these approaches do not adequately capture the aggressive nature of T1HG BC. Thus, new, more accurate biomarkers for T1HG risk stratification are needed. Here, we enrolled three different patient cohorts and investigated expression of collagen type VI alpha 1 (COL6A1), a key component of the extracellular matrix, at different stages and grades of BC, with a specific focus on T1HG BC. Materials and Methods: Samples from 298 BC patients were subjected to RNA sequencing and real-time polymerase chain reaction. Results: We found that T1HG BC and muscle invasive BC (MIBC) exhibited comparable expression of COL6A1, which was significantly higher than that by other NMIBC subtypes. In particular, T1HG patients who later progressed to MIBC had considerably higher expression of COL6A1 than Ta, T1 low grade patients, and patients that did not progress, highlighting the aggressive nature and higher risk of progression associated with T1HG BC. Moreover, Cox and Kaplan–Meier survival analyses revealed a significant association between elevated expression of COL6A1 and poor progression-free survival of T1HG BC patients (multivariate Cox hazard ratio, 16.812; 95% confidence interval, 3.283–86.095; p=0.001 and p=0.0002 [log-rank test]). Conclusions These findings suggest that COL6A1 may be a promising biomarker for risk stratification of T1HG BC, offering valuable insight into disease prognosis and guidance of personalized treatment decisions.

Objective The aim of this study was to explore the application of baseline neutrophil-lymphocyte ratio(NLR),platelet count-lymphocyte ratio(PLR),monocyte-lymphocyte ratio(MLR),and pan-immune inflammation value(PIV)in the use of PD-1 inhibitors combined with chemotherapy in advanced non-small cell lung cancer(NSCLC),and establish a prognosis-related nomogram model.Methods The clinical data of 77 patients with driver gene-negative advanced NSCLC who received first-line PD-1 inhibitor combined with chemotherapy at Harbin Medical University Cancer Hospital from January 2019 to January 2021 were retro-spectively analyzed.Univariate and multivariate Cox regression analysis were used to determine the independent prognostic factors of progression-free survival(PFS);A prognostic-related nomogram model was established,and the accuracy of prediction model was e-valuated through consistency index.Results Multivariate Cox regression analyses showed that MLR,PIV,brain metastasis,and pleu-ral metastasis were independent factors affecting PFS in patients with driver gene-negative advanced NSCLC(P<0.05).The nomo-gram prognostic model constructed based on the Cox regression results had a good predictive ability(C-index value was 0.786,95%CI:0.721-0.851).The ROC curve showed that the combined effect of MLR and PIV in detecting the prognosis of PFS(AUC=0.717,P=0.001)was better than that of MLR(AUC=0.643)and PIV(AUC=0.640).Conclusion MLR,PIV,brain metastasis,and pleural metastasis can predict the prognosis of driver gene-negative advanced NSCLC patients treated with first-line chemothera-py combined with PD-1 inhibitors.The established nomogram model has high accuracy and clinical practicability.The predictive per-formance of combined detection of MLR and PIV may be better than that of separate detection of MLR and PIV.

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

Objective:To assess causes for revision total knee arthroplasty (TKA) in China using the data of revision TKA in the past 15 years in our single center andcompare the differences in survival time, operation time and blood loss among different revision reasons.Methods:Data of 337 patients (345 knees) with revision TKAs at our institution from January 2007 to December 2021 (15 years) were retrospectively analyzed. The included population consists of 57 males and 288 females. The causes for first revision TKA were identified and compared according to the time of revision surgery as early (up to 2 years) and late revision (more than 2 years). The reason for revision before 2012 and after 2012 was also compared. Furthermore, the differences of survival time, operation time and blood loss among different revision reasons were compared.Results:The most common reasons for revision of knee joints in 345 cases were periprosthetic infection (133 knees, 38.6%), followed by aseptic loosening (97 knees, 28.1%) and joint instability (35 knees, 10.1%). Early revisions were performed in 171 knees (49.6%), while late revisions were performed in 174 knees (50.4%). Periprosthetic infection (96 knees, 56.1%) and aseptic loosening (86 knees, 49.4%) were the most common reasons for early and late revisions, respectively. There were 59 revisions performed before 2012 and 286 revisions performed after 2012, with periprosthetic infection being the main reason for revision in both groups. The percentage of revisions due to infection decreased from 64.4% before 2012 to 33.2% after 2012, and this difference was statistically significant (χ 2=18.790, P<0.001). The proportion of revisions due to aseptic loosening was 15.3% before 2012, which was significantly lower than the proportion of 30.8% after 2012 (χ 2=5.083, P=0.024). The median survival time of the prostheses in the included patients was 30 months, with shorter survival time observed in patients with stiffness, patellar complications, and periprosthetic infection, and longer survival time observed in patients with polyethylene wear and aseptic loosening. There were significant differences in operation time and blood loss among different reasons for revision ( P<0.001). Conclusion:In our specialized arthroplasty center periprosthesis infection was the most common reason for revision. Periprosthesis infection and aseptic loosening needed to be considered for early or late-stage revision. With the development of technique of total knee arthroplasty, the proportion of periprosthesis infection is decreasing, while the incidence of aseptic loosening is increasing.

ObjectiveTo study the bioactive secondary metabolites of Talaromyces sp. TP21 and their bioactivities. MethodThe secondary metabolites of Talaromyces sp. TP21 were isolated by high performance liquid chromatography （HPLC）， normal phase and reversed phase column chromatography combined with molecular networking and bioassay-guided fractionation， and their structures were determined by nuclear magnetic resonance （NMR） and high resolution mass spectrometry （HR MS）. The inhibitory effects of the compounds on the growth of the lung cancer cell line A549 and the liver cancer cell line Hep G2 were measured by themethyl thiazolyl tetrazolium （MTT） method. The antimicrobial activities of the compounds were measured with Staphylococcus aureus and human oral cavity-derived Saccharomyces cerevisiae as the indicator microorganisms. ResultSeventeen compounds were isolated from the secondary metabolites of Talaromyces sp. TP21 and identified as ergochrome C （1）， daldiniaeschsone A （2）， seco-blennolide B （3）， penitholabene （4）， penicichrysogene A （5）， orsellinic acid （6）， griseofulvin （7）， isorhodoptilometrin （8）， （+）-5-chloromitorubrinic acid （9）， penicillixanthone A （10）， pentacecilide B （11）， pentacecilide C （12）， chrodrimanin C （13）， chrodrimanin E （14）， chrodrimanin H （15）， chrodrimanin F （16）， and 3-hydroxypentacecilide A （17）. ConclusionCompounds 1-5， 11-12， and 17 were isolated from Talaromyces for the first time. Among them， compounds 4， 7， and 10-12 exhibited inhibitory activities against the growth of A549 and Hep G2 cells， with the median inhibitory concentration below 50 μmol·L^-1. Furthermore， compounds 9 and 10 showed inhibitory activities against S. aureus and human oral cavity-derived S. cerevisiae， with the minimum inhibitory concentration of 8-128 mg·L^-1.