Objective To construct glucose oxidase（GOx）–loaded nanogels （GONGs）, optimize their formulation, and evaluate their capacity to inhibit the Warburg effect in glioma cells. Methods A responsive polymer （HAM） was synthesized and used to self-assemble GONGs, which were then characterized. Encapsulation efficiency and drug loading were determined using fluorescence spectrophotometry. Biocompatibility was tested by measuring cytotoxicity and hemolytic activity. Western blotting was used to evaluate the effects of GONGs on the expression of proteins associated with the Warburg phenotype and oxidative damage in glioma cells. Results GONGs prepared at a drug–to–polymer ratio of 1∶10 exhibited a particle size of 140.3 nm and a zeta potential of −27.2 mV. Compared with free GOx, GONGs markedly reduced cytotoxicity, increased the IC₅₀ in hUVEC cells from 2.150 nmol/L to 74.86 nmol/L, and significantly decreased hemolysis. At a GOx concentration of 2 nmol/L, GONGs effectively downregulated glycolysis-related proteins, such as HK2 and LDHA, and inhibited glutamine metabolism in glioma cells. Conclusion GONGs exhibited high GOx loading capacity, significantly reduced GOx-induced cytotoxicity, inhibited the Warburg effect in glioma cells and induced oxidative damage.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis （CIP） based on the theory of "cough attributed to the five zang （脏） organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs"， drug toxicity triggers cancer toxin， leading to disharmony among the five zang organs， and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore， treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice， CIP can be classified into four syndrome patterns， including lung yin depletion， deficiency of both the lung and the spleen with phlegm-dampness， liver fire harassing the lung， and lung-kidney yin deficiency. Correspondingly， Chaimai Jinluo Runfei Decoction （柴麦金络润肺汤） is used to nourish yin and moisten the lung； Qigui Peitu Huayin Decoction （芪桂培土化饮汤） is used to fortify the spleen and tonify the lung， resolve dampness and dispel phlegm； Chaidan Shuyu Runjin Decoction （柴丹疏郁润金汤） is used to drain liver and clear the lung； and Dimai Jinshui Xiangsheng Decoction （地脉金水相生汤） is used to nourish the kidney and moisten the lung.

Objective To explore the clinical characteristics,laboratory examination indicators,and auxilia-ry examination results of critically ill children with adenovirus pneumonia,screen relevant indicators with warning effects for critically ill children with adenovirus pneumonia,and construct an early identification scale for critically ill children with adenovirus pneumonia.Methods The clinical data of totally 86 children with adenovirus pneumonia admitted in the hospital from May 2021 to September 2023 were retrospectively ana-lyzed,and multivariate Logistic regression analysis was used to screen relevant indicators for the early identifi-cation of severe adenovirus pneumonia in children.The sensitivity and the specificity were analyzed using the receiver operating characteristic(ROC)curve.Experts conducted a quantitative evaluation of the weight scores of each factor,and finally an early identification scale for critically ill children with adenovirus pneumo-nia was developed.Results Among 86 children with severe adenovirus pneumonia,34 were critically ill with adenovirus pneumonia.There were statistically significant differences in the incidence of respiratory distress,respiratory distress,consciousness and behavior disorders,respiratory symptoms,cardiovascular symptoms,and neurological symptoms between the two groups(P<0.05).The differences of white blood cell count,platelet count,erythrocyte dynamic sedimentation rate,serum ferritin,serum ferritin/erythrocyte dynamic sed-imentation rate,R-glutamyltransferase,alanine aminotransferase,lactate dehydrogenase between the severe group and the critically ill group were statistically significant(P<0.05).Multivariate Logistic regression a-nalysis showed that white blood cell count,platelet count,alanine aminotransferase,serum ferritin/erythrocyte dynamic sedimentation rate and lactate dehydrogenase were all influencing factors for the progression to criti-cal illness in children with adenovirus pneumonia(P<0.05),and the ROC curve results showed that the area under the curve of the diagnostic model composed of white blood cell count,platelet count,alanine aminotrans-ferase,serum ferritin/red blood cell dynamic sedimentation rate,and lactate dehydrogenase for diagnosing crit-ical illness was 0.864,and the sensitivity and the specificity were 86.42%and 82.76%,respectively.After 25 peer experts evaluated the weight scores of various clinical manifestations and examination items,the early i-dentification scale for critically ill children with adenovirus pneumonia was finally developed.Conclusion Dur-ing clinical treatment,the clinical manifestations of children with adenovirus pneumonia can be considered in conjunction with relevant auxiliary examination results,and early identification scales can be used to determine whether children with adenovirus pneumonia are at risk of developing into critical illness.

To summarize Professor DING Ying's clinical experience in treating children's IgA nephropathy from the perspective of "wind-induced water turbidity". It is believed that the core pathogenesis of IgA nephropathy in children is the wind stimμlating water to become turbidity， and the basic treatment principles are to eliminate wind and settle viscera， and to remove turbidity and drain water. For those with the syndrome of wind-heat invading the lungs and injury to blood collaterals， modified Yinqiao Powder （银翘散） combined with Xiaoji Decoction （小蓟饮子） could be used； for those with dampness-heat in Sanjiao， heavy dampness and light heat pattern， modified Sanren Decoction （三仁汤） combined with Bazheng Powder （八正散） could be used； for those with lung-spleen qi deficiency and kidney essence depletion pattern， modified Buzhong Yiqi Decoction （补中益气汤） combined with Wuzi Yanzong Pill （五子衍宗丸） could be used； for those with deficiency of both qi and yin， kidney deficiency with stasis pattern， self-prescribed Yishen Huazhuo Formula （益肾化浊方） could be used. Meanwhile on the basis of pattern identification and treatment， rattan-type herbs could be combined in use in order to unblock the meridians and collaterals.

AIM: To compare the agreement between the ARK Biometer Combo and OA 2000 in patients wearing orthokeratology lenses.METHODS: A prospective study. A total of 148 patients(148 eyes)who were wearing orthokeratology lenses and returned for follow-up at the Shanghai Eye Disease Prevention and Treatment Center from August to September 2024 were included. Biometric measurements were performed using both the ARK Biometer Combo and OA 2000. Parameters including axial length(AL), corneal central thickness(CCT), anterior chamber depth(ACD), lens thickness(LT), corneal curvature(Kf and Ks), astigmatism(AST), white-to-white corneal diameter(WTW)and pupil diameter(PD)were obtained. Differences in measurement parameters between the two biometers were compared, and agreement was assessed.RESULTS: There were no statistically significant differences in the measurements of Kf, Ks and AST between the two biometers(P>0.05). Statistically significant differences were found in the measurements of AL, CCT, ACD, LT, WTW and PD(t=2.559, P=0.012; t=16.771, P<0.0001; t=4.749, P<0.0001; t=-15.212, P<0.0001; t=-14.915, P<0.0001; t=-2.402, P=0.018). ICC ranged from 0.615 to 0.999. Bland-Altman analysis showed that the maximum absolute values of the 95% limits of agreement(LoA)of AL, CCT, ACD, LT, Kf, Ks, AST, WTW and PD were 0.07 mm, 35.07 μm, 0.07 mm, 0.12 mm, 0.66 D, 1.14 D, 1.00 D, 0.76 mm, and 0.98 mm, respectively.CONCLUSION: In orthokeratology patients, the ARK Biometer Combo and OA 2000 showed good agreement in measuring AL, CCT, ACD, Kf and LT, and can be used interchangeably.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

While multiple step saccades (MSS) are occasionally reported in the healthy population, they are more evident in patients with Parkinson's disease (PD). Therefore, MSS has been suggested as a biological marker for the diagnosis of PD. However, the lack of clarity on the neural mechanism underlying the generation of MSS largely impedes their application in the clinic. We have proposed recently that MSS are triggered by the discrepancy between desired and executed saccades. Accordingly, brain regions involved in saccadic planning and execution might play a role in the generation of MSS. To test this hypothesis, we explored the role of the prefrontal (PFC) and posterior parietal cortex (PPC) in generating MSS by conducting two experiments: electroencephalographic recording and single-pulse transcranial magnetic stimulation in the PFC or PPC of humans while participants were performing a gap saccade task. We found that the PFC and PPC are involved in the generation of MSS.
Humans ; Parietal Lobe/physiology* ; Saccades/physiology* ; Prefrontal Cortex/physiology* ; Male ; Transcranial Magnetic Stimulation ; Female ; Electroencephalography ; Adult ; Young Adult

The increasing aging population and aging-associated diseases have become a global issue for decades. People over 65 show an increased prevalence and greater severity of periodontitis, which poses threats to overall health. Studies have demonstrated a significant association between aging and the dysfunction of neutrophils, critical cells in the early stages of periodontitis, and their crosstalk with macrophages and T and B lymphocytes to establish the periodontal lesion. Neutrophils differentiate and mature in the bone marrow before entering the circulation; during an infection, they are recruited to infected tissues guided by the signal from chemokines and cytokines to eliminate invading pathogens. Neutrophils are crucial in maintaining a balanced response between host and microbes to prevent periodontal diseases in periodontal tissues. The impacts of aging on neutrophils' chemotaxis, anti-microbial function, cell activation, and lifespan result in impaired neutrophil functions and excessive neutrophil activation, which could influence periodontitis course. We summarize the roles of neutrophils in periodontal diseases and the aging-related impacts on neutrophil functional responses. We also explore the underlying mechanisms that can contribute to periodontitis manifestation in aging. This review could help us better understand the pathogenesis of periodontitis, which could offer novel therapeutic targets for periodontitis.
Humans ; Neutrophils/immunology* ; Periodontitis/immunology* ; Aging/physiology*

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*