Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.

Objectives:To investigate the enhancement of tumor penetration and photodynamic therapy (PDT) efficacy in triple-negative breast cancer by hyaluronidase (HAase) using a novel pH-responsive IR780-loaded photosensitive micelle.Methods:The pH-responsive IR780-loaded photosensitive micelles were prepared using the nanoprecipitation method, and their morphology, size, and encapsulation efficiency were characterized. The in vitro stability and pH-responsive drug release of the micelles were also evaluated. The cytotoxicity of the micelles on triple-negative breast cancer cells (MDA-MB-231) was assessed using a cell counting kit. A nude mouse breast cancer model was established, and HAase was injected intratumorally 24 hours before intravenous injection of the photosensitive micelles. The effect of HAase on the biodistribution and tumor uptake of the micelles was detected using small animal in vivo imaging. CD31 and HIF-1α immunofluorescence staining were performed to investigate the mechanism of HAase-enhanced tumor penetration. The body weight and tumor volume of the mice were measured, and necrosis and apoptosis of tumor tissues were assessed using HE staining and TUNEL staining, respectively. Results:Transmission electron microscopy showed that the micelles had a uniform particle size of approximately 60-70 nm, with a hydrated particle size of (98.03±0.22) nm. The IR780 encapsulation efficiency was 74.15%, with a drug loading content of 2.07%. After 7 days at 4 ℃, there was no significant change in hydrated particle size ( P=0.062). The 24-hour release rates of the micelles in PBS at pH 7.4 and 6.5 were (2.41±0.21)% and (43.69±2.09)%, respectively, showing a significant difference ( P＜0.000 1). The cytotoxicity assay revealed that the cell viability in the micelles group without light exposure was significantly higer than that in the micelles group under light exposure [(97.00±5.38)% vs. (53.27±9.00)%, P=0.000 2]. The micelles were able to target and accumulate in the tumor tissue, and this accumulation increased significantly with HAase treatment. CD31 and HIF-1α immunofluorescence staining indicated that the CD31 signal was enhanced [(0.27±0.05)% vs. (4.57±0.27)%, P＜0.000 1] and the HIF-1α signal was reduced [(5.14±0.38)% vs. (0.08±0.04)%, P＜0.000 1] in the HAase-treated group compared to that in the micelle-only group. After 11 days of treatment with HAase combined with photosensitive micelles, there was no statistically significant difference in mouse body weight ( P＞0.05). However, the tumor volume inhibition rate in the HAase-micelle-mediated PDT group was significantly higher than that in the micelle-mediated PDT group [(87.66±6.37)% vs. (25.34±12.63)%, P=0.002]. Histological staining showed a significant increase in tumor cell necrosis and apoptosis in the HAase-micelle-mediated PDT group. Conclusion:HAase enhances the deep tumor penetration and targeted accumulation of pH-responsive IR780-loaded photosensitive micelles, significantly improves the efficacy of photodynamic therapy in triple-negative breast cancer.

Objective:To analyze the molecular characteristics of prevalent Bordetella pertussis (Bp) isolates in Liaocheng City, Shandong Province in 2024. Methods:From March to August 2024, oropharyngeal swabs were collected from suspected pertussis cases at Liaocheng People′s Hospital in Shandong Province for Bp isolation. A total of 99 Bp isolates were obtained. Whole-genome sequencing was performed on all isolates, followed by Multilocus Sequence Typing (MLST), vaccine antigen-related gene typing (including ptxP, ptxA, ptxB, ptxC, ptxD, ptxE, fhaB, fim2, fim3, and prn), 23S rRNA gene typing, and phylogenetic analysis. To capture the differences between Bp isolates and vaccine strains in Liaocheng City, the international vaccine strain Tohama I and the Chinese vaccine strain CS were included in the analysis. Antimicrobial resistance testing against 11 agents was performed on 52 isolates. Results:The throat swabs of 99 Bp isolates were collected from patients aged 44 days to 42 years, and the median age of the patients was 7 (5, 8) years. All isolates ptxP were ptxP3 type. 74 isolates (74.75%) carried the prn150, while 21 isolates (21.21%) were prn-deficient. The predominant antigenic profile was ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150, found in 72 isolates (72.73%). All 99 isolates carried the A2047G mutation in the 23S rRNA gene. Antimicrobial susceptibility testing showed that the MICs of macrolides and clindamycin for all 52 Bp isolates were all >256 mg/L. However, the isolates showed low MIC for seven other antimicrobials tested, including trimethoprim-sulfamethoxazole, amoxicillin, and levofloxacin. MLST typing revealed that 94 isolates (94.95%) were identified as ST-2, while 5 isolates (5.05%) belonged to a novel sequence type (ST-118). Phylogenetic analysis demonstrated that all 99 Bp isolates were highly homologous but clustered in evolutionary branches distinct from vaccine strains. Conclusion:In 2024, Bordetella pertussis isolates in Liaocheng City exhibit distinct clonal epidemic characteristics, with the predominant antigenic genotype being ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150. All isolates are resistant to macrolide antibiotics.

Objective:To construct a measurement index system for the high-quality development of public traditional Chinese medicine (TCM) hospitals and conduct an analysis of the coupling coordination degree, providing a reference for the high-quality development of public TCM hospitals.Methods:The characteristics and principles for the high-quality development of public TCM hospitals were conceptualized and operationalized based on the new development philosophy. The Delphi method was adopted to establish a coupled and coordinated measurement index system for the high-quality development of public TCM hospitals. The empirical study was conducted using the data from 240 teritiary grade A public TCM hospitals at the manicipal level and above in 2022, selected from the comprehensive statistical system of the Monitoring and Statistical Research Center. The comprehensive evaluation index method was adopted to comprehensively evaluate the level of high-quality development, and the coupling coordination degree model was used to calculate the level of coupling coordination development.Results:The constructed measurement index system for the high-quality development of public TCM hospitals included 5 first-level indicators (inheritance and innovation, service quality improvement, efficient operation, element openness, and resource sharing), 10 second-level indicators and 32 third-level indicators. The 240 public TCM hospitals basically presented a development level state of resource sharing>element openness>efficient operation>service quality improvement>inheritance and innovation in the subsystem dimensions. The average coupling coordination degree among subsystems was 0.498, which belonged to the primary coordination stage. The coupling coordination degree of element opening and resource sharing with other subsystems was relatively high, while the coupling coordination degree of inheritance and innovation with other subsystems was relatively low.Conclusions:The role of inheritance and innovation in driving the development of public TCM hospitals still needs to be improved. There are significant differences in the coupling and coordination degree among subsystems. It is suggested that the capacity building of advantageous specialties in TCM be further strengthened, the quality and level of services be improved, the regional coordinated development strategy of public TCM hospitals be further implemented, the regional development gap be narrowed, and the coordinated development of various subsystems of high-quality public TCM hospitals be promoted.

Objective:To investigate the impact of evaluating the alcohol intake on all-cause mortality in patients with metabolic-associated fatty liver disease（MAFLD）and metabolic dysfunction and alcohol-related liver disease（MetALD）.Method:The retrospective study included patients aged 20 to 74 years with hepatic steatosis diagnosed by ultrasound，with data from the Third National Health and Nutrition Examination Survey（NHANES III）between 1988 and 1994. Participants were categorized into light，moderate，and heavy drinking groups according to daily alcohol intake. Multivariable-adjusted hazard ratios（aHR）and their 95% confidence intervals（ CI）were calculated by Cox proportional risk regression modeling to assess the effect of alcohol intake on all-cause mortality. Results:A total of 2 322 patients were included in the study. Males accounted for 50.2%（1 166/2 322），with a age of 42.0（31.3，57.0）years，a median follow-up of 316.0（270.0，337.0）months，and an all-cause mortality rate of 1.48% per person-year. There were 1，763 cases in the light drinking group，333 in the moderate drinking group，and 226 in the heavy drinking group.The all-cause mortality rates for patients in the three drinking groups were 1.38%，1.67%，and 2.10% per person-year，respectively. The moderate（a HR=1.37，95% CI：1.12 to 1.67， P=0.002）and heavy（a HR=1.45，95% CI：1.17 to 1.80， P=0.001）drinking groups were independently associated with increased all-cause mortality following covariate adjustment. There was a difference in all-cause mortality for alcohol intake in non-type 2 diabetes mellitus（T2DM）patients under 60 years of age（ P<0.05），but the difference was not statistically significant between non-T2DM patients over 60 years of age and T2DM patients of all ages（ P>0.05）according to the analysis of diabetes status and age subgroups. Conclusion:Alcohol intake has a dose-dependent negative effect on patients with MAFLD and MetALD. The risk of all-cause mortality increased significantly with increasing alcohol intake.

Objective To explore clinical effect of accessory scaphoid bone fusion in treating type Ⅱ painful accessory scaphoid bone.Methods A retrospective analysis was performed on 26 patients with type Ⅱ painful accessory navicular bone treated by accessory navicular bone fusion from January 2012 to June 2022,including 1 male and 25 females,aged from 18 to 70 years old with an average of(44.61±16.32)years old;10 patients with type Ⅱ A and 16 patients with type Ⅱ B;20 patients with simple fusion and 6 patients with fusion plus calcaneal translocation osteotomy.Changes of Meary angle,Pitch angle,an-teroposterior talar-first metatarsal angle(T1MA),talonavicular coverage angle(TCA),lateral talocalcaneal angle(LTCA)be-fore operation and 6 months after operation were observed and compared,and American Orthopedic Foot and Ankle Society(AOFAS)foot and ankle score and visual analogue scale(VAS)were used to explore clinical effect.Results All 26 patients were followed up for 7 to 24 months with an average of(10.72±3.94)months.Meary angle,Pitch angle,T1MA,TCA and LTCA were improved from(9.20±2.57)°,(16.45±3.57)°,(33.34±5.02)°,(22.42±5.86)°,(48.89±4.43)° before opertaion to(3.33±1.06)°,(22.33±4.56)°,(23.89±3.48)°,(11.83±2.67)°,(36.50±3.50)° at 6 months after operation,the difference were statistically significant(P＜0.01).Postoperative AOFAS foot and ankle score were(86.24±4.33)and(93.18±6.02)for type Ⅱ A and type Ⅱ B at 6 months,which were significantly improved compared with those for type Ⅱ A and type Ⅱ B before op-eration(67.34±6.55)and(65.12±9.51),and the difference was statistically significant(P＜0.01);20 patients got excellent re-sult,5 good and 1 poor.Preoperative VAS of type ⅡA(5.67±1.58)and type Ⅱ B(5.77±1.49)were improved to(2.13±1.01)and(1.43±0.68)at 6 months after operation,with statistical significance(P＜0.01).Conclusion Fusion of accessory navicular bone in patients with type Ⅱ painful accessory navicular bone combined with internal calcaneal osteotomy in patients with par-tial calcaneal valvaration could effectively correct flat foot deformity and relieve pain,and could be used as a clinical treatment for painful accessory navicular bone.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

Objective:To observe and analyze the short-term effects of intravitreal injection of Conbercept (IVC) on the expression levels of matrix metalloproteinase (MMP)-2 and MMP inhibitor-2 (TIMP-2) in the aqueous humor of eyes with proliferative diabetic retinopathy (PDR).Methods:A prospective clinical study. From March 2024 to June 2024, 30 consecutive patients with 30 eyes with PDR (PDR group) undergoing IVC combined with pars plana vitrectomy (PPV) at Department of Ophthalmology of The First Affiliated Hospital of University of Science and Technology were included in the study, along with 20 patients with 20 eyes undergoing cataract surgery (control group) during the same period. In the PDR group, IVC treatment was performed 3 to 7 days before PPV, and 0.05-0.10 ml aqueous humor was collected before IVC and before PPV. In the control group, 0.05-0.10 ml aqueous humor was collected before cataract surgery. The levels of vascular endothelial growth factor (VEGF), MMP-2, and TIMP-2 in the aqueous humor were measured using enzyme-linked immunosorbent assay. For normally distributed data, independent samples t-test were used for comparison between two groups; for non-normally distributed data, the Mann-Whitney U test was used. The correlation analysis of VEGF, MMP-2, TIMP-2 concentrations in aqueous humor of PDR patients was performed using Pearson's correlation coefficient. Results:There were no statistically significant differences in age ( Z=-1.810) and gender composition ( χ2=3.450) between the PDR group and the control group ( P>0.05). Before IVC, VEGF and MMP-2 expression levels were (0.23±0.10), (2.11±1.32) ng/ml and (0.12±0.03), (0.53±0.26) ng/ml in patients' aqueous fluid in PDR group and control group, respectively. The expression level of TIMP-2 and the ratio of MMP-2/TIMP-2 were (0.99±0.26), (1.76±0.11) ng/ml and 2.04 (1.19, 2.98), 0.36 (0.15, 0.39), respectively. Compared with the control group, the expression levels of VEGF and MMP-2 in aqueous humor in PDR group ( t=-5.030, -5.260) and the ratio of MMP-2/TIMP-2 ( Z=-5.740) were significantly increased, with statistical significance ( P<0.01). The expression level of TIMP-2 was significantly lower than that of control group, the difference was statistically significant ( t=12.120, P<0.01). After IVC, the expression levels of VEGF and MMP-2 in aqueous humor of PDR patients were (0.13±0.03) and (2.11±1.32) ng/ml, respectively. The expression level of TIMP-2 and the ratio of MMP-2/TIMP-2 were (0.95±0.28) ng/ml and 1.57 (1.02, 3.13), respectively. Compared with before IVC, the expression level of VEGF in aqueous humor in PDR group after IVC was significantly decreased, and the difference was statistically significant ( t=6.080, P<0.01). The expression levels of MMP-2 ( t=1.220), TIMP-2 ( t=0.290) and the ratio of MMP-2/TIMP-2 ( Z=-0.260) were not significantly different ( P=0.270, 0.780, 0.800). After IVC, there was no significant difference in VEGF expression level between PDR group and control group ( t=-1.200, P=0.240). The expression level of MMP-2 was still significantly increased ( t=-5.880), the expression level of TIMP-2 was still significantly decreased ( t=11.520), and the ratio of MMP-2/TIMP-2 was still significantly increased ( Z=-5.780), with statistical significance ( P<0.01). Correlation analysis showed that VEGF was positively correlated with MMP-2 in aqueous humor of PDR patients before IVC ( r=0.590, P<0.01). Conclusions:IVC can effectively reduce the level of VEGF in the aqueous humor of eyes with PDR in the short term, but it has no significant effect on the levels of MMP-2 and TIMP-2.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

Post-stroke spasticity is a series of symptoms after stroke,such as hand and foot urgency,unflexion and extension of muscles,etc.In order to deeply understand the cognition of post-stroke spasticity of ancient Chinese physicians and comb out their therapeutic thoughts,this study took the General Catalogue of Chinese Ancient Books of Traditional Chinese Medicine as a bibliographic reference,all the ancient Chinese literature on spasms after stroke was retrieved manually and by computer,and then sorted and analyzed,and classified them by longitudinal time,and extracted the description about post-stroke spasticity,including medical classics,prescriptions,clinical evidence,medical records and so on.And this paper verified and summarized the etiology,pathogenesis,functional and indications and prescription characteristics of spasticity after stroke,in order to deeply understand systematic theories and treatment ideas of the ancient medical practitioners in the bud,development and mature stages of their understanding of spasticity after stroke,and provide the theoretical basis for the later doctors to understand this disease and the modern clinical treatment of traditional Chinese medicine.