ObjectiveTo conduct sarcopenia-related screening and assessment among community-dwelling elderly patients with type 2 diabetes mellitus (T2DM) in Changning District of Shanghai, to analyze the current status and influencing factors of suspected sarcopenia in this population, and to provide references for the early prevention and treatment of sarcopenia. MethodsUsing a stratified random sampling method, elderly T2DM patients under management in the Chronic Disease Health Management System of Changning District in Shanghai were selected as the study subjects. Patients were screened for sarcopenia and underwent related health examinations according to the Chinese Expert Consensus on Diagnosis and Treatment of Sarcopenia in the Elderly (2021). Self-designed questionnaires were used to collect basic information, lifestyle habits and health status, and the Montreal Cognitive Assessment (MoCA) was employed to evaluate cognitive function. ResultsAmong 758 elderly patients with T2DM [average age: (72.19±6.19) years old], 214 patients were identified as having suspected sarcopenia,accounting for 28.23%. The proportion of suspected sarcopenia was higher in females (30.94%) than in males (24.08%) (χ²=4.20, P=0.040), and higher in older patients (χ²=22.26, P<0.001). Higher proportions of suspected sarcopenia were also observed among patients who followed a vegetarian diet (39.77%) (χ²=73.28, P=0.011), had diabetic foot (59.09%) (χ²=10.65, P=0.001), reported feeling fatigued most of the time (37.11%) (χ²=4.33, P=0.037), or had mild cognitive impairment (χ²=3.95, P=0.047). The duration of T2DM in the suspected sarcopenia group [(12.86±10.07) years old] was longer than that in the non-sarcopenia group [(9.73±8.63) years old] (t=3.79, P<0.001), and the average body mass index (BMI) in the suspected sarcopenia group [(22.17±2.45) kg⋅m^-²)] was lower than that in the non-sarcopenia group [(25.11±3.26) kg⋅m^-²)] (t=-11.41, P<0.001). Multivariate logistic regression analyses showed that older age (OR=1.08, 95%CI:1.047‒1.110) and longer duration of T2DM (OR=1.02, 95%CI:1.005‒1.043) were associated with a higher risk of suspected sarcopenia in elderly T2DM patients. Female elderly T2DM patients had a higher risk of suspected sarcopenia (OR=1.89, 95%CI:1.310‒2.733) than males, and those with diabetic foot (OR=3.66, 95%CI:1.341‒9.990) had a higher risk than those without diabetic foot. ConclusionThe proportion of elderly T2DM patients with suspected sarcopenia was relatively high. In community-based integrated health management, healthcare providers should pay more attention to elderly T2DM patients who are older, have longer disease duration, are female, or have diabetic foot, so as to identify risks early and implement targeted comprehensive interventions and health management.

ObjectiveTo assess the performance of preoperative serum Golgi protein 73 （GP73） in diagnosing liver fibrosis degree in patients with resectable hepatocellular carcinoma （HCC）， to investigate its value in predicting postoperative survival， and to provide a basis for risk stratification and individualized decision-making in this population. MethodsA total of 631 patients with HCC who underwent liver resection at The First Hospital of Jilin University from March 1， 2009 to December 31， 2022 were enrolled. The demographic， pathological， and serological features of the patients were collected， and the serum level of GP73 was measured before surgery. Scheuer score determined by liver biopsy was used as the gold standard for diagnosing liver fibrosis； the Spearman correlation analysis was used to investigate the correlation between GP73 and liver fibrosis； the receiver operating characteristic （ROC） curve and the area under the ROC curve （AUC） were used to assess the value of serum GP73 and compound serological markers in the diagnosis of liver fibrosis， and the Delong test was used for comparison of AUC. With all-cause mortality as the outcome， X-Tile 3.6.1 software was used to determine the optimal cut-off value of GP73； the univariate and multivariate Cox regression analyses were used to identify independent influencing factors for prognosis， and a nomogram model was constructed. Ten-fold cross-validation was used for internal validation； index of concordance （C-index）， integrated discrimination improvement （IDI） index， and net reclassification improvement （NRI） index were calculated； calibration curve and decision curve analysis were used to assess the predictive performance of the model. ResultsThe serum level of GP73 was positively correlated with Scheuer liver fibrosis stage （r_s=0.255， P<0.001）. Serum GP73 had a significantly higher AUC than gamma-glutamyl transferase-to-platelet ratio （0.704 vs 0.634， Z=2.00， P=0.046） and S index （0.704 vs 0.637， Z=1.98， P=0.048） in the diagnosis of significant liver fibrosis， with no significant difference compared with aspartate aminotransferase-to-platelet ratio index （AUC=0.722） and fibrosis-4 index （AUC=0.695） （both P>0.05）. During a median follow-up time of 48.66 months， 239 patients （37.9%） died. GP73 had an optimal cut-off value of 65 ng/mL in predicting postoperative mortality in patients with resectable HCC， and high GP73 expression （≥65 ng/mL） alone achieved a C-index of 0.617 for predicting the prognosis of HCC patients， which was better than the C-index of 0.551 for Barcelona Clinic Liver Cancer （BCLC） stage （P<0.001）. The multivariate Cox regression analysis showed that serum GP73 （hazard ratio ［HR］=2.56， 95% confidence interval ［CI］： 1.86 — 3.52， P<0.001）， sex （HR=1.58， 95%CI： 1.10 — 2.28， P=0.014）， vascular invasion （HR=1.69， 95%CI： 1.30 — 2.21， P<0.001）， total bilirubin （HR=1.49， 95%CI： 1.16 — 1.93， P=0.002）， and maximum tumor diameter （HR=1.07， 95%CI： 1.04 — 1.11， P<0.001） were independent risk factors for all-cause mortality after hepatectomy in patients with HCC. In order to assess whether the addition of GP73 to the other four variables could further improve model performance， the model based on GP73， sex， vascular invasion， total bilirubin， and maximum tumor diameter was defined as the GP73-included model， and the model based on all five variables except GP73 was defined as the GP73-excluded model. The GP73-included model achieved an AUC of 0.704 （95%CI： 0.656 — 0.753） for predicting 5-year survival rate after surgery， and ten-fold cross-validation showed that this model had a mean C-index of 0.716 （95%CI： 0.682 — 0.750）， which was higher than the C-index of the GP73-excluded model （C-index=0.682， 95%CI： 0.645 — 0.719， P=0.008） and BCLC stage （C-index=0.551， 95%CI： 0.523 — 0.580， P<0.001）. Compared with the GP73-excluded model， the GP73-included model yielded an IDI index of 0.039 （95%CI： 0.016 — 0.069， P<0.001） and an NRI index of 0.259 （95%CI： 0.179 — 0.335， P<0.001）， and compared with BCLC stage， the GP73-included model had an IDI index of 0.112 （95%CI： 0.069 — 0.163， P<0.001） and an NRI index of 0.272 （95%CI： 0.169 — 0.380， P<0.001）. Calibration curve and decision curve analyses showed that the GP73-included model had good calibration and net clinical benefit. ConclusionGP73 can be used as a serological biomarker for diagnosing liver fibrosis in patients with resectable HCC， and preoperative GP73 level has a certain value in predicting the survival of these patients after hepatectomy. The integrated prognostic model incorporating GP73 can help to optimize postoperative risk stratification， thereby providing a basis for decision-making in precise treatment of HCC.

Objective:To apply statistical process control (SPC) techniques to the quality assurance of non-normal radiotherapy plans through Johnson transformation, establishing patient-specific tolerance and action limits based on treatment sites and dose/distance assessment criteria, thereby enhancing the intensity-modulated radiation therapy (IMRT) verification accuracy and dose delivery precision.Methods:In this study, 951 gamma analysis data of patient-specific quality assurance (PSQA) executed on the Halcyon accelerator platform were selected and categorized into six groups based on treatment sites, including brain (102 cases), head and neck (100 cases), breast (229 cases), lung (154 cases), esophagus (223 cases), and pelvic (143 cases) groups. The six groups of data were statistically analyzed through Anderson-Darling normality tests ( α = 0.05) using Minitab 21 software. Non-normal data were transformed into normal data through Johnson transformation and then were used to establish treatment site-specific tolerance and action limits, which were compared with the Shewhart control charts based on normal distributions. Results:The PSQA result of the six groups all exhibited non-normal distributions ( P < 0.05). Through Johnson transformation, the tolerance and action limits for the head and neck, breast, lung, esophagus, and pelvic areas under the 3%/2 mm criterion ranged from 95.13% to 96.16% and 94.19% to 95.91%, respectively. In contrast, the tolerance and action limits ranged from 91.15% to 94.86% and 89.94% to 94.78% under the 2%/2 mm criterion. Directly applying Shewhart control charts without normality assumptions yielded higher tolerance limits compared to the application of Johnson transformation, increasing the false positive rate in the non-normal PSQA process. Conclusions:Applying the SPC techniques directly to a non-normal process can lead to an increased false alarm rate and wrong process interpretation. The SPC techniques combined with Johnson transformation enable more effective monitoring of a non-normal PSQA process, facilitating timely identification of potential factors that may lead to an out-of-control process based on the treatment site-specific limits.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To evaluate the association between heatwaves and fall-related mortality.Methods:A total of 61 421 fall-related mortality from 2013 to 2022 in 7 provinces of China were included in a time-stratified case-crossover design, with daily meteorological data derived from the fifth generation European Reanalysis dataset produced by the European Centre for Medium-Range Weather Forecasts. Conditional logistic regression chimeric distributed lag nonlinear model was used to analyze the association between heatwaves and fall-related mortality and stratified analysis was conducted according to gender and age.Results:Heatwaves were associated with an increased risk of fall-related morality. The risk of fall-related mortality during heatwaves was higher than during non-heatwave periods ( OR=1.11, 95% CI: 1.05-1.18). The attributable fraction of fall-related motality due to heatwaves was 10.25% (95% CI: 4.49%-15.36%). For each 1 ℃ increase above the heatwave threshold, the risk of fall-related mortality increased by 34% ( OR=1.34, 95% CI: 1.02-1.76). The effect of heatwave duration on fall-related mortality was not statistically significant. Stratified analyses indicated that women experienced a higher risk of fall-related mortality during heatwaves ( OR=1.13, 95% CI: 1.04-1.22) compared to man ( OR=1.10, 95% CI: 1.04-1.17). Conclusions:Heatwave increases the risk of fall-related mortality, and the intensity of heatwaves modify this risk. Women are vulnerable populations.

Objective:To compare the application effects of upper arm autogenous arteriovenous fistula (AVF) and forearm arteriovenous graft (AVG) in maintenance hemodialysis (MHD) patients, and to analyze the factors influencing the long-term patency rate of arteriovenous fistulas in MHD patients.Methods:It was a retrospective cohort study. The data of MHD patients treated in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2021 to May 2023 was collected. Participants were stratified into two groups: forearm AVG and upper arm AVF. The parameters including urea clearance index (Kt/V), serum C-reactive protein (CRP), albumin levels, access-related costs, complication rates, and long-term primary patency were compared. The end event was defined as arteriovenous fistula failure, that was, the arteriovenous fistula could not be used for dialysis puncture, or the arteriovenous fistula lost function after adequate blood flow was achieved. Kaplan-Meier survival curves with log-rank tests were employed to compare access survival, while multivariable Cox regression was used to analyze the independent associated factors of patency.Results:A total of 71 MHD patients were enrolled in this study, including 35 males, with age of (64.9±11.7) years and fistula establishment time of 30.0(17.0, 58.0) months. There were 32 cases (45.1%) in the forearm AVG group and 39 cases (54.9%) in the upper arm AVF group. Compared with the forearm AVG group, the upper arm AVF group had higher serum albumin levels [38.9 (37.0, 42.1) g/L vs. 38.0 (34.6, 40.0) g/L, Z=-2.364, P=0.018], higher pain scores [3.0(2.0, 5.0) points vs. 2.0(1.0, 3.0) points, Z=-3.012, P=0.003], and higher long-term patency rates of arteriovenous fistulas (at 3, 6, 12, and 24 months, all P<0.01), while the complication rate[61.5% (24/39) vs. 93.7% (30/32), χ2=10.015, P=0.002], the cost of the access [0 (0, 9,117.0) yuan·year -1·person -1vs. 10 380.5 (7 186.0, 30 228.5) yuan·year -1·person -1, Z=-4.094, P<0.001] were lower, and the length of the available puncture vessel segment was shorter [3.5(3.0, 5.0) cm vs. 6.5(6.0, 8.0) cm, Z=-6.477, P<0.001].The Kaplan-Meier survival analysis results showed that the primary patency rate of the upper arm AVF group was significantly higher than that of the forearm AVG group (Log-rank test, χ2=23.690, P<0.001). The multivariate Cox regression analysis results indicated that the type of fistula being forearm AVG (with upper arm AVF as reference, HR=4.907, 95% CI 1.740-13.840) and increased complications number ( HR=1.234, 95% CI 1.040-1.464) were the independent factors promoting the arteriovenous fistula failure in MHD patients. Conclusions:The type of internal fistula and the complications are the factors affecting the long-term patency rate of internal fistula in MHD patients.Upper arm AVF offers cost-effectiveness and sustained patency advantages over forearm AVG but requires careful consideration of puncture challenges and patient discomfort. Individualized access selection should balance anatomical constraints with clinical priorities.

Objective:To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and 24-h urinary calcium excretion (24-h UCaE) and hypercalciuria in Chinese adults.Methods:This cross-sectional study was conducted from March 2022 to March 2023 in nine cities in China and included 1 239 residents. Demographic characteristics were collected through questionnaires and physical examinations, fasting blood samples were assessed for bone metabolism indicators, and 24-h urine samples were used to determine the 24-h UCaE. Multiple linear regression analysis was used to explore the relationship between serum 25(OH)D and 24-h UCaE and bone metabolism indexes. The relationship between serum 25(OH)D and hypercalciuria was analyzed using a multiple logistic regression model combined with restricted cubic spline modeling.Results:The mean participant age was (47.9±18.1) years, of which 453 (36.6%) were male. The percentages of vitamin D sufficiency, insufficiency, and deficiency were 7.6% (94/1 239), 29.0% (359/1 239), and 63.4% (786/1 239), respectively. The multiple linear regression model showed that after adjusting for the covariates the 24-h UCaE gradually increased with higher levels of 25(OH)D ( P overall <0.001, P nonlinear <0.001). The logistic regression analysis revealed that compared with the vitamin D deficient group, the OR for the prevalence of hypercalciuria in the vitamin D sufficient and vitamin D insufficient groups were 3.290 (95% CI 1.745 to 6.202) and 3.742 (95% CI 2.458 to 5.697), respectively. The results of the restricted cubic spline modeling showed a positive nonlinear relationship between 25(OH)D and the prevalence of hypercalciuria ( P overall <0.001, P nonlinear <0.001). The prevalence of hypercalciuria increased when 25(OH)D was >17.00 μg/L and peaked at 26.71 μg/L, after which there was a decreasing trend in the prevalence of hypercalciuria with increasing 25(OH)D. Conclusion:Associations between serum 25(OH)D levels and urinary calcium excretion and the prevalence of hypercalciuria were observed in the Chinese adult population.

A novel analytical method was developed in this study by combining online solid phase extraction with ultra performance liquid chromatography-tandem mass spectrometry(Online SPE-UPLC-MS/MS)for simultaneous determination of 50 kinds of steroid hormones in surface water.Specifically,after high-speed centrifugation of 4 mL water samples,the supernatant was directly injected into an Oasis HLB online SPE column for enrichment and purification.Subsequently,the target compounds were transferred to the analytical column via valve switching for separation and analysis.The chromatographic separation was performed on a Thermo Acclaim RSLC C18 column(100 mm×2.1 mm,2.2 μm),using a mobile phase composed of 5 mmol/L ammonium fluoride aqueous solution and acetonitrile.Mass spectrometric detection was conducted in positive ion mode,utilizing multiple reaction monitoring(MRM)with quantification achieved by the internal standard method.The method validation demonstrated that the limits of detection(LOD)for the 50 kinds of steroid hormones ranged from 0.02 to 0.50 ng/L,while the limits of quantification(LOQ)were between 0.08 and 1.67 ng/L.The average recoveries in surface water samples at spiked concentrations of 5,20 and 200 ng/L were between 74.1％and 119％,with relative standard deviations(RSDs)of 0.2％to 9.9％.This method was applied to analyze 11 surface water samples collected from sites surrounding a pharmaceutical and chemical industrial park.A total of 44 kinds of steroid hormones were detected,with concentrations ranging from 0.11 to 88.6 ng/L,revealing the presence of hormone contamination in the environmental waters surrounding industrial areas.Compared with the traditional offline SPE methods,the proposed online SPE technique significantly reduced sample volume requirements and pretreatment time,while minimizing the loss of target compounds during the pretreatment process.Moreover,compared to reported online SPE techniques,this method achieved high-throughput analysis of multiple classes of steroid hormones,with lower detection limits and higher recoveries.Overall,this method provided rapid sample preparation,high sensitivity,and excellent stability,making it suitable for the direct analysis of trace steroid hormones in surface water.

OBJECTIVES: To study the clinical characteristics, efficacy, and prognosis of pediatric Langerhans cell histiocytosis (LCH). METHODS: A retrospective analysis was conducted on 72 children with newly diagnosed LCH. RESULTS: The median age of the 72 children was 5 years (range: 0-14 years), with skull involvement being the most common (56 cases, 77.8%). The BRAF-V600E mutation was not associated with clinical characteristics, efficacy, or prognosis (P>0.05). The 5-year overall survival rate was 91.6%±4.2%, and the 5-year event-free survival (EFS) rate was 67.5%±5.8%. The 6-week chemotherapy response rate and 5-year EFS rate were lower in the risk organ involvement group compared to the no risk organ involvement group (P<0.05). The five-year overall survival rates for the group with multi-system involvement and the group with platelet count ≥450×10⁹/L were respectively lower than those for the single-system involvement group and the group with platelet count <450×10⁹/L (P<0.05). Risk organ involvement is an independent risk factor for 5-year EFS (P<0.05). CONCLUSIONS Skull is the most commonly affected site in pediatric LCH. The BRAF-V600E mutation is not related to clinical characteristics, efficacy, or prognosis. Elevated platelet count, risk organ involvement, and multisystem involvement are associated with poor prognosis, with risk organ involvement being an independent risk factor for 5-year EFS.
Humans ; Histiocytosis, Langerhans-Cell/therapy* ; Child, Preschool ; Child ; Male ; Infant ; Female ; Adolescent ; Retrospective Studies ; Proto-Oncogene Proteins B-raf/genetics* ; Prognosis ; Infant, Newborn ; Mutation

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.