OBJECTIVE To screen a single matrix， prepare dissolving microneedles of Pterocarya hupehensis total flavonoids（PHTF-MN）， and characterize it while evaluating its analgesic effects.METHODS Using microneedle morphology and puncture rate as evaluation indicators， the matrix was screened from polyvinyl alcohol （PVA）， polyvinylpyrrolidone K30 （PVP K30）， PVP K90， and sodium hyaluronate with relative molecular weights of 15 000 and 60 000 （HA 1.5w and HA 6w ）. PHTF-MN was prepared by the layer-by-layer casting method with the selected matrix， and the appearance and morphology， total flavonoid content， mechanical properties， puncture performance， dissolution properties， and drug release behavior of the obtained PHTF-MN were characterized. Using male BALB/c mice as test subjects and aspirin （ASA） as a positive control， the analgesic effects of the microneedles were evaluated using a formalin-induced pain model.RESULTS Blank microneedles prepared with 30% HA 1.5w exhibited optimal surface flatness and the membrane puncture rate （through 4 layers of parafilm membrane） reaching 78%. The PHTF-MNs （with PHTF contents of 10， 20， 30， 40， and 50 mg/g in the matrix） exhibited uniform arrays and intact tips， with RSDs for total flavonoid contents all below 7% （ n ＝8）. The single-needle puncture forces were 1.46 and 1.07 N （with PHTF contents of 30 and 50 mg/g in the matrix， respectively）. The skin penetration rate approached 100%， with visible puncture marks in the stratum corneum and drug residue （with a PHTF content of 50 mg/g in the matrix）. After 30 min of fixation， the needles had almost completely dissolved， and the skin retention rates all exceeded 90% （with PHTF contents of 10， 30， and 50 mg/g in the matrix， respectively）. The cumulative release within 8 h was （134.64±2.03） μg/cm 2 ， and the fit to the first-order kinetic equation （ R 2 ＝0.950 1） was highest （with a PHTF content of 50 mg/g in the matrix）. Low- and high-dose PHTF-MN （containing 85.26 and 145.03 μg of total flavonoids per patch， respectively； 1 patch/day） significantly shortened the cumulative time of phase Ⅱ pain response in mice （ P ＜0.05）， with pain inhibition rates （43.67% and 59.78%） comparable to those of ASA （53.70%）.CONCLUSIONS PHTF-MN using HA 1.5w as a single matrix was successfully prepared. This formulation features a simplified preparation process， uniform drug loading， favorable mechanical properties， resistance to fracture， and rapid dissolution. Its drug release behavior conforms to a first-order kinetic model， and its analgesic effect is comparable to that of ASA.

AIM:To explore the feasibility of predicting orthokeratology lens ordering parameters(flat K, spherical power, lens diameter, and lens toricity)using the extreme gradient boosting(XGBoost)algorithm based on corneal topographic parameters and basic clinical examination indicators, and to provide references for intelligent clinical fitting.METHODS:Clinical data were retrospectively collected from myopic patients who underwent initial orthokeratology lens fitting and achieved successful fitting at Puyang Second People's Hospital between January 2019 and March 2024. Data from right and left eyes were treated as independent samples, and the dataset was partitioned at the patient level into training and test sets in a 7∶3 ratio. Input features included uncorrected visual acuity(UCVA), axial length(AL), horizontal visible iris diameter(HVID), flat K, steep K, horizontal eccentricity, and vertical eccentricity. The lens toricity prediction model additionally incorporated keratometric astigmatism(ΔK)and surface asymmetry index(SAI). The output labels were the final ordering parameters(flat K, spherical power, lens diameter, and lens toricity). Separate XGBoost regression models were constructed for each output parameter, with hyperparameters optimized independently through grid search combined with 5-fold cross-validation. Model performance was evaluated on the test set using the coefficient of determination(R2), mean absolute error(MAE), and root mean square error(RMSE). Feature importance analysis was also performed.RESULTS:Totally 400 patients(800 eyes)were included in the final analysis. The 400 patients comprised 208 male(52.0%)and 192 female(48.0%)patients, with a mean age of 10.1±2.3 y. After partitioning at the patient level, the training set comprised 280 patients(560 eyes; 146 males and 134 females; mean age 10.1±2.3 y), and the test set comprised 120 patients(240 eyes; 62 males and 58 females; mean age 10.0±2.2 y). No statistically significant differences in sex composition or age were found between the two sets(P>0.05). Toric lenses were used by 140 of the 280 patients(50.0%)in the training set and by 50 of the 120 patients(41.7%)in the test set(χ2=2.017, P=0.156). The flat K prediction model achieved an MAE of 0.34 D and an R2 of 0.84. The spherical power model attained an MAE of 0.43 D and an R2 of 0.70. The lens diameter model yielded an MAE of 0.12 mm and an R2 of 0.42. The lens toricity model(Tweedie regression, power=1.5)achieved an MAE of 0.44 D and an R2 of 0.38. The MAE for each parameter fell within the clinically acceptable tolerance limits(flat K≤0.50 D, spherical power ≤0.75 D, lens diameter ≤0.25 mm, lens toricity ≤0.75 D). Scatter plots and Bland-Altman analysis demonstrated strong agreement between predicted values and actual observations. Feature importance analysis revealed that flat K(0.70)and steep K(0.11)were the most influential predictors in the flat K prediction model.CONCLUSION: The XGBoost model based on routine clinical parameters provides predictions of flat K, spherical power, and lens diameter with MAEs within clinically acceptable ranges, and offers useful reference for cylindrical power prediction. This approach may serve as a useful adjunct to clinical lens fitting. Nevertheless, future prospective studies are warranted to validate its clinical utility in improving actual fitting success rates.

[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective To analyze the mutation status of Kirsten rat sarcoma viral oncogene homolog(KRAS),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),v-raf murine sarcoma viral oncogene homolog B1(BRAF)genes,and the expression of mismatch repair(MMR)and human epidermal growth factor receptor 2(HER-2)proteins in tumor tissues of patients with colorectal cancer(CRC)harboring neuroblastoma rat sarcoma viral oncogene homolog(NRAS)gene mutations,and explore their relationships with the clinicopathological characteristics of CRC patients.Methods The clinicopathological data of 546 patients with NRAS mutation CRC were retrospectively analyzed.The mutation status of NRAS,KRAS,PIK3CA,and BRAF genes was detected by AmoyDx amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)kit(fluorescent PCR method),the expression levels of MMR and HER-2 proteins were detected by immunohistochemical staining EnVision method,and the relationship between them and the clinicopathological characteristics of patients were analyzed.Results The mutation rate of single-point mutations in the NRAS gene was 98.35%(537/546),double-point mutations in the NRAS gene were 1.65%(9/546),and double mutations in the NRAS and KRAS genes were 1.47%(8/546).No patients were found to harbor mutations in the PIK3CA or BRAF genes.The types of NRAS mutations included Q61R(or Q61K,Q61L,Q61H)mutations(266/546,48.72%),G12D(or G12S)mutations(154/546,28.21%),G13R(or G12C,G12V,G12A,G13V)mutations(134/546,24.54%),and A146T mutation(1/546,0.18%).G13R(or G12C,G12V,G12A,G13V)mutations in the NRAS gene were more likely to occur in the rectum cancer patients(P=0.035);although the tumors had a larger diameter(P=0.029),the patients had a longer progression-free survival after surgery(P=0.028).Among patients with NRAS gene mutations,HER-2 positive expression was associated with perineural invasion(P=0.003),and the patients with deficient MMR were younger on average(P=0.041)and were associated with double-point mutations in the NRAS gene(P=0.018).Conclusion CRC harboring NRAS mutations may have unique clinicopathological characteristics and molecular phenotypes,providing possibilities for individualized treatment and prognosis evaluation of CRC.

With the increasing demand for dynamic,real-time and rapid qualitative analysis of chemical composition in areas such as emergency response and space exploration,chip-scale mass spectrometers have attracted significant attention.These devices are expected to drive the integration of mass spectrometry with micro/nano-fabrication and intelligent sensing technologies,fostering profound innovation and breakthroughs in analytical chemistry.As an excellent mass analyzer,the ion trap exhibits numerous advantages,and its miniaturization creates favorable conditions for the high-density integration of miniature mass spectrometers.However,the reduction in ion storage capacity may compromise its sensitivity and dynamic range,rendering the study of ion unidirectional ejection in highly miniaturized ion traps of significant practical importance.In this work,a research was conducted on achieving efficient ion unidirectional ejection while maintaining high mass resolution in the extremely miniature hyperbolic linear ion trap(M-HLIT)with a field radius of 1 mm,and an electric field compensation method was proposed,which combined asymmetric electrode stretching and unbalanced RF voltage to achieve high-precision optimization of the electric field composition.Simulations showed that in an ideal structure,this method achieved 100％unidirectional ejection efficiency with the mass resolution of 518,significantly outperforming traditional asymmetric structure method(365)and unbalanced voltage method(321).Following the introduction of ion ejection slots,further optimization through bidirectional stretching and electrical parameters improved the resolution to 790 while maintaining a unidirectional ejection efficiency of 93％.This method eliminated the requirement for additional excitation voltage,offering an ideal solution for the miniature mass analyzer with high detection performance of chip-level mass spectrometers.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective:To investigate the intervention effect of five elements music of traditional Chinese medicine and western classical music on the sleep quality of stroke patients, and to compare the difference between the two, to provide a reference for the clinical care measures to improve the sleep quality of stroke patients.Methods:By adopting a randomized controlled trial, 75 stroke patients who were hospitalized in the rehabilitation hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from July 2022 to July 2023 were selected by convenience sampling method as the study subjects, and the patients were randomly divided the conventional treatment group, the five-element music group, and the classical music group according to the method of randomized numerical table with 25 cases in each group. On the basis of general treatment, the conventional treatment group took sleep health education, the five elements music group were given five-element music intervention based on conventional treatment, and the classical music group were given classical music intervention based on conventional treatment. The changes of Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) examination parameters in the 3 groups were compared.Results:There were 2 cases of shedding in the conventional treatment group, and 23 cases were finally included, 15 males and 8 females, aged (54.02 ± 7.80) years; there were no cases of shedding in the five-element music group, and 25 cases were finally included, 12 males and 13 females, aged (53.69 ± 6.02) years; and there was 1 case of shedding in the classical music group, and 24 cases were finally included, 10 males and 14 females, aged (52.34 ± 7.08) years. Comparison of AIS, PSQI and PSG scores among the 3 groups of patients before intervention showed no statistically significant differences (all P>0.05). After the intervention, the AIS scores and PSQI scores of the 3 groups were (9.48 ± 1.53) and (12.22 ± 2.94), (6.76 ± 1.36) and (7.64 ± 2.08), (7.46 ± 1.38) and (10.33 ± 2.82), respectively, and the differences were statistically significant ( F=23.21, 18.44, both P<0.05). PSG sleep structure parameters showed that the total sleep time, REM latency time and sleep efficiency of the patients in the five-element music group after the intervention were (399.89 ± 51.76) min, (136.26 ± 25.36) min, (78.87 ± 8.21)%, higher than (368.45 ± 47.88) min, (124.46 ± 26.25) min, (73.36 ± 7.86)% in the classical music group and (345.48 ± 38.69) min, (111.37 ± 23.23) min, (69.44 ± 7.88)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=8.27, 5.93, and 8.49, all P<0.05); the sleep latency time, awakening time, and number of awakenings in the five-element music group were (28.86 ± 17.68) min, (54.37 ± 25.15) min, and (2.72 ± 1.19) times, respectively, which were lower than those in the classical music group (35.67 ± 16.99) min, (64.28 ± 29.34) min, and (3.67 ± 1.12) times and (42.38 ± 18.96) min, (78.38 ± 37.26) min, (4.87 ± 1.46) times in the conventional treatment group, and the differences between three groups were statistically significant ( F=3.51, 3.66, and 17.56, all P<0.05). The results of the PSG sleep progression showed that the duration of the N1 stage of sleep in the five-element music group after the intervention was (95.71 ± 15.23) min, which was higher than (83.20 ± 18.34) min in the classical music group and (80.93 ± 16.47) min in the conventional treatment group, and the difference between three groups was statistically significant ( F=5.53, P<0.01); the N3 stage sleep time and the sleep percentage of the five-element music group after the intervention were respectively (84.23 ± 20.98) min and (23.98 ± 5.89)%, which were higher than (65.33 ± 18.82) min and (18.34 ± 3.78)% in the classical music group and (45.87 ± 18.65) min and (15.03 ± 5.56)% in the conventional treatment group, and the differences between three groups were statistically significant ( F=23.08, 18.50, both P<0.05). Conclusions:Both five elements music and classical music can improve the sleep quality of stroke patients, and the effect of five elements music to improve sleep is more significant.

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of elderly patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of elderly DLBCL patients diagnosed pathologically between 2010 and 2015 were extracted from the SEER database. Cox proportional hazards model was used for multivariate analysis, and Kaplan-Meier survival curves were plotted to explore the prognostic factors affecting overall survival (OS). RESULTS: A total of 11 523 elderly DLBCL patients were included, of whom 58.6% had stage Ⅲ/Ⅳ disease, and 28.8% exhibited extranodal involvement. Besides lymph nodes (68.5%), common primary extranodal sites included the gastrointestinal tract (9.8%) and lip, mouth, and pharynx (4.1%). The median survival time for the entire cohort was 47 months, with a 3-year survival rate of 52.0%, and a 5-year survival rate of 47.8%. Multivariate Cox regression analysis revealed that age, sex, race, Ann Arbor stage, primary site, B symptoms, treatment modality, treatment sequence, and whether DLBCL was the first malignant primary indicator were independent prognostic factors affecting OS in elderly DLBCL patients (all P <0.05). CONCLUSION Age≥70 years, male, black race, advanced Ann Arbor stage, primary sites in the lungs, liver, or kidney, presence of B symptoms, and preoperative systemic therapy were independent risk factors for poor prognosis in elderly DLBCL patients.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Prognosis ; Aged ; Male ; Female ; Survival Rate ; Proportional Hazards Models ; Aged, 80 and over ; Kaplan-Meier Estimate ; Neoplasm Staging