Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Cold tumors have a poor response to tumor immunotherapy due to low immune cell infiltration and the ability to evade immune attacks. Converting cold tumors into hot tumors can enhance the clinical effectiveness of anti-tumor immunotherapy. High-intensity focused ultrasound (HIFU) as a non-invasive treatment can damage tumors through mechanical effects, but there is a lack of research on its cytotoxic mechanisms at the cellular level and its role in inducing anti-immune responses. In this study, the role of HIFU in triggering tumor ferroptosis by disrupting the GSH/GSSG balance through mechanochemical action and the associated anti-tumor immune priming effect were investigated. The use of a nano-enhancer loaded with PFOB combined with HIFU could enhance ferroptosis in triple-negative breast cancer at a specific stage of tumor growth (UTGR = 0) while promoting the conversion of a cold tumor into a hot tumor, thereby improving the immune response. Overall, this provides valuable guidance for the clinical application of HIFU in tumor immunotherapy.

OBJECTIVE: To investigate the application value of pediatric sepsis-induced coagulation (pSIC) score and mean platelet volume/platelet count (MPV/PLT) ratio in the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis. METHODS: A retrospective cohort study was conducted, selecting 112 children with sepsis (sepsis group) admitted to pediatric intensive care unit (PICU) of Liaocheng Second People's Hospital from January 2020 to December 2023 as the study objects, and 50 children without sepsis admitted to the pediatric surgery department of our hospital during the same period for elective surgery due to inguinal hernia as the control (control group). The children with sepsis were divided into two groups according to the pediatric critical case score (PCIS). The children with PCIS score of ≤ 80 were classified as critically ill group, and those with PCIS score of > 80 was classified as non-critically ill group. pSIC score, coagulation indicators [prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and fibrinogen (FIB)], and platelet related indicators (PLT, MPV, and MPV/PLT ratio) were collected. Pearson correlation method was used to analyze the correlation between pSIC score and MPV/PLT ratio as well as their correlation with coagulation indicators. Multivariate Logistic regression analysis was used to screen the independent risk factors for pediatric sepsis and critical pediatric sepsis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the application value of the above independent risk factors on the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis. RESULTS: 112 children with sepsis and 50 children without sepsis were enrolled in the final analysis. pSIC score, PT, INR, APTT, FIB, MPV, and MPV/PLT ratio in the sepsis group were significantly higher than those in the control group [pSIC score: 0.93±0.10 vs. 0.06±0.03, PT (s): 14.76±0.38 vs. 12.23±0.15, INR: 1.26±0.03 vs. 1.06±0.01, APTT (s): 40.08±0.94 vs. 32.47±0.54, FIB (g/L): 3.51±0.11 vs. 2.31±0.06, MPV (fL): 8.86±0.14 vs. 7.62±0.11, MPV/PLT ratio: 0.037±0.003 vs. 0.022±0.001, all P < 0.01], and PLT was slightly lower than that in the control group (×10⁹/L: 306.00±11.01 vs. 345.90±10.57, P > 0.05). Among 112 children with sepsis, 46 were critically ill and 66 were non-critically ill. pSIC score, PT, INR, APTT, MPV, and MPV/PLT ratio in the critically ill group were significantly higher than those in the non-critically ill group [pSIC score: 1.74±0.17 vs. 0.36±0.07, PT (s): 16.55±0.80 vs. 13.52±0.23, INR: 1.39±0.07 vs. 1.17±0.02, APTT (s): 43.83±1.72 vs. 37.77±0.95, MPV (fL): 9.31±0.23 vs. 8.55±0.16, MPV/PLT ratio: 0.051±0.006 vs. 0.027±0.001, all P < 0.05], PLT was significantly lower than that in the non-critically ill group (×10⁹/L: 260.50±18.89 vs. 337.70±11.90, P < 0.01), and FIB was slightly lower than that in the non-critically ill group (g/L: 3.28±0.19 vs. 3.67±0.14, P > 0.05). Correlation analysis showed that pSIC score was significantly positively correlated with MPV/PLT ratio and coagulation indicators including PT, APTT and INR in pediatric sepsis (r value was 0.583, 0.571, 0.296 and 0.518, respectively, all P < 0.01), and MPV/PLT ratio was also significantly positively correlated with PT, APTT and INR (r value was 0.300, 0.203 and 0.307, respectively, all P < 0.05). Multivariate Logistic regression analysis showed that pSIC score and MPV/PLT ratio were independent risk factors for pediatric sepsis and critical pediatric sepsis [pediatric sepsis: odds ratio (OR) and 95% confidence interval (95%CI) for pSIC score was 14.117 (4.190-47.555), and the OR value and 95%CI for MPV/PLT ratio was 1.128 (1.059-1.202), both P < 0.01; critical pediatric sepsis: the OR value and 95%CI for pSIC score was 8.142 (3.672-18.050), and the OR value and 95%CI for MPV/PLT ratio was 1.068 (1.028-1.109), all P < 0.01]. ROC curve analysis showed that pSIC score and MPV/PLT ratio had certain application value in the diagnosis of pediatric sepsis [area under the ROC curve (AUC) and 95%CI was 0.754 (0.700-0.808) and 0.720 (0.643-0.798), respectively] and the determination of critical pediatric sepsis [AUC and 95%CI was 0.849 (0.778-0.919) and 0.731 (0.632-0.830)], and the combined AUC of the two indictors was 0.815 (95%CI was 0.751-0.879) and 0.872 (95%CI was 0.806-0.938), respectively. CONCLUSIONS pSIC score and MPV/PLT ratio have potential application value in the diagnosis of pediatric sepsis and the determination of critical pediatric sepsis, and the combined application of both is more valuable.
Humans ; Sepsis/complications* ; Platelet Count ; Mean Platelet Volume ; Retrospective Studies ; Child ; Blood Coagulation Disorders/diagnosis* ; Intensive Care Units, Pediatric ; Male ; Female ; Partial Thromboplastin Time ; Child, Preschool ; Blood Coagulation ; International Normalized Ratio ; Infant

YABBY proteins are important transcription factors that regulate morphogenesis and organ development in plants. In order to study the YABBY of strawberry, bioinformatic technique were used to identify the YABBY gene families in Fragaria vesca (diploid) and Fragaria×ananassa (octoploid), and then analyze the sequence characters, phylogeny and collinearity of the family members. The RNA-seq data and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique were used to assay the expression patterns of the family members. A green fluorescent protein (GFP) was fused with FvYABBYs and transiently expressed in tobacco leaf cells for the subcellular localization. As the results, six FvYABBY genes and 26 FxaYABBY genes were identified from F. vesca and F.×ananassa, respectively. The FvYABBY genes were grouped into five clades, and five family members were orthologous with AtYABBY genes of Arabidopsis. In F. vesca, all of the FvYABBYs were basically not expressed not expressed in root and receptacle, while FvYABBY1, FvYABBY2, FvYABBY5 and FvYABBY6 were highly expressed in leaf, shoot, flower and achene. In F.×ananassa, FxaYABBY1, FxaYABBY2, FxaYABBY5 and FxaYABBY6 were expressed in achene, and all FxaYABBY were poorly or not expressed in receptacle. Additionally, under the abiotic stresses of low temperature, high salt and drought, the expression of FvYABBY1, FvYABBY3, FvYABBY4 and FvYABBY6 were down-regulated, FvYABBY5 was up-regulated, and FvYABBY2 was up-regulated and then down-regulated. In tobacco leaf cells, the subcellular localization of FvYABBY proteins were in the nucleus. These results provides a foundation for the functional researches of YABBY gene in strawberry.
Fragaria/genetics* ; Arabidopsis ; Biological Assay ; Cold Temperature ; Computational Biology

SUN gene is a group of key genes regulating plant growth and development. Here, SUN gene families of strawberry were identified from the genome of the diploid Fragaria vesca, and their physicochemical properties, genes structure, evolution and genes expression were also analyzed. Our results showed that there were thirty-one FvSUN genes in F. vesca and the FvSUNs encoded proteins were classified into seven groups, and the members in the same group showed high similarity in gene structures and conservative motifs. The electronic subcellular localization of FvSUNs was mainly in the nucleus. Collinearity analysis showed that the members of FvSUN gene family were mainly expanded by segmental duplication in F. vesca, and Arabidopsis and F. vesca shared twenty-three pairs of orthologous SUN genes. According to the expression pattern in different tissues shown by the transcriptome data of F. vesca, the FvSUNs gene can be divided into three types: (1) expressed in nearly all tissues, (2) hardly expressed in any tissues, and (3) expressed in special tissues. The gene expression pattern of FvSUNs was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the seedlings of F. vesca were treated by different abiotic stresses, and the expression level of 31 FvSUNs genes were assayed by qRT-PCR. The expression of most of the tested genes was induced by cold, high salt or drought stress. Our studies may facilitate revealing the biological function and molecular mechanism of SUN genes in strawberry.
Fragaria/metabolism* ; Genes, Plant ; Stress, Physiological/genetics* ; Arabidopsis/genetics* ; Plant Development ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism*

GLKs (GOLDEN 2-LIKEs) are a group of plant-specific transcription factors regulating the chloroplast biogenesis, differentiation and function maintains by triggering the expression of the photosynthesis-associated nuclear genes (PhANGs). The GLKs also play important roles in nutrient's accumulation in fruits, leaf senescence, immunity and abiotic stress response. The expression of GLK genes were affected by multiple hormones or environmental factors. Therefore, GLKs were considered as the key nodes of regulatory network in plant cells, and potential candidates to improve the photosynthetic capacity of crops. Since numerous researches of GLKs have been reported in plants, the biological function, molecular mechanism of GLKs genes and its applications in breeding were summarized and a GLK-mediated signaling network model was developed. This review may facilitate future research and application of GLKs.
Chloroplasts/genetics* ; Gene Expression Regulation, Plant ; Photosynthesis/genetics* ; Plant Breeding ; Transcription Factors/metabolism*

Objective:To explore the effect of shoulder subluxation on the peripheral nerves in the hemiplegic upper limbs of stroke survivors.Methods:Twenty stroke survivors with shoulder subluxation were enrolled. Conduction in their suprascapular, axillary, musculocutaneous, radial, median and ulnar nerves was monitored and needle electromyography was used to monitor activity in the supraspinatus, deltoid, biceps brachii, extensor digitorum, abductor pollicis brevis and abductor digiti minimi muscles of their affected upper limbs at rest. Upper limb and hand function were assessed using the Brunnstrom scale. The rate of change in the amplitude of the compound muscle action potentials (CMAPs) was correlated with the patient′s disease duration, age, and upper limb and hand Brunnstrom stages.Results:Compared with the healthy side, a significant decrease was observed in the CMAP amplitudes of the suprascapular, axillary, musculocutaneous, radial, median and ulnar nerves of the hemiplegic arm, and the latency of the suprascapular and axillary nerves was significantly prolonged. There was no inter-arm difference in the conduction velocity of the musculocutaneous, radial, median and ulnar nerves. The rates of change in the CMAP amplitudes of the suprascapular, axillary and musculocutaneous nerves were significantly higher than those of the radial, median and ulnar nerves. The sensory nerve action potential (SNAP) amplitudes of the median, ulnar and radial nerves on the hemiplegic side were significantly lower than on the healthy side, but there was no significant difference in the sensory conduction velocity between the two sides. On the hemiplegic side, the median nerve had the highest rate of change rate in the SNAP amplitude, followed by the radial and ulnar nerves, but there was no significant difference among them. Nor was there any significant difference in the rate of change in sensory nerve conduction velocity. The muscles of the affected upper limbs had higher potentials in the proximal than that in the distal nerves after shoulder subluxation. The rate of change in the CMAPs was not significantly correlated with a patient′s disease duration, age, or upper limb or hand Brunnstrom stage on the hemiplegic side.Conclusions:Shoulder subluxation after a stroke can cause greater damage to the peripheral nerves in the shoulder and upper arm than to those in the forearm and hand, possibly affecting the recovery of upper limb function.

Objective:To evaluate the clinical value and effect of the application of computer navigation system in orbital-zygomatic fibrous dysplasia.Methods:From March 2016 to December 2018, 16 patients with orbital-zygomatic fibrous dysplasia admitted to Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine were included in this study. CT scans and computer aided designs were finished preoperatively. By mirrored and compared with the healthy side, preoperative-designed lesion removal area was determined and surgical regions were highlighted. Digital reference frame was fixed rigidly to patient’s forehead. After accurate registration, lesion area was removed with the aid of surgical navigation system according to preoperative-designed plan restrictively through lower eyelid-intraoral approach. The symmetric morphology of orbital-zygomatic region was analyzed postoperatively. Zygomaxillare, oribitale, zygomaticand lower orbital point of zygomatic maxillary were marked both in preoperative and postoperative three-dimensional reconstructions, and the distance between them and mid-sagittal plane was measured. Paired- t tests were applied in this study for symmetric analysis. Results:In this study, 16 patients with orbital zygomatic bone fiber dysplasia assisted by computer navigation were included, consisted of 12 males and 4 females, ranging from 18 years old to 35 years old. The differences of preoperative symmetric analysis in zygomaxillare, oribitale, zygomatic had statistical significance( P<0.01). The difference of preoperative symmetric analysis in lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The differences of postoperative symmetric analysis in zygomaxillare, oribitale, zygomatic and lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The difference in zygomaxillare decreased from(10.1±6.2) mm to(2.7±6.4) mm. The difference in oribitale(ORI)decreased from(7.7±4.6) mm to(1.9±3.9) mm. The difference in zygomatic decreased from(8.5±7.5) mm to(0.7±1.5)mm. The difference in lower orbital point of zygomatic maxillary decreased from(1.9±3.5) mm to(0.6±2.1) mm. The morphology of the affected side and the healthy side was symmetrical. The contour was natural and no postoperative complications occurred. The postoperative satisfaction rate was high. Conclusions:Computer navigation system can solve the problem of limited exposure of lower eyelid-intraoral approach in orbital-zygomatic fibrous dysplasia and significantly improve the accuracy, effectiveness and safety during surgery.

Objective:To evaluate the clinical value and effect of the application of computer navigation system in orbital-zygomatic fibrous dysplasia.Methods:From March 2016 to December 2018, 16 patients with orbital-zygomatic fibrous dysplasia admitted to Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine were included in this study. CT scans and computer aided designs were finished preoperatively. By mirrored and compared with the healthy side, preoperative-designed lesion removal area was determined and surgical regions were highlighted. Digital reference frame was fixed rigidly to patient’s forehead. After accurate registration, lesion area was removed with the aid of surgical navigation system according to preoperative-designed plan restrictively through lower eyelid-intraoral approach. The symmetric morphology of orbital-zygomatic region was analyzed postoperatively. Zygomaxillare, oribitale, zygomaticand lower orbital point of zygomatic maxillary were marked both in preoperative and postoperative three-dimensional reconstructions, and the distance between them and mid-sagittal plane was measured. Paired- t tests were applied in this study for symmetric analysis. Results:In this study, 16 patients with orbital zygomatic bone fiber dysplasia assisted by computer navigation were included, consisted of 12 males and 4 females, ranging from 18 years old to 35 years old. The differences of preoperative symmetric analysis in zygomaxillare, oribitale, zygomatic had statistical significance( P<0.01). The difference of preoperative symmetric analysis in lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The differences of postoperative symmetric analysis in zygomaxillare, oribitale, zygomatic and lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The difference in zygomaxillare decreased from(10.1±6.2) mm to(2.7±6.4) mm. The difference in oribitale(ORI)decreased from(7.7±4.6) mm to(1.9±3.9) mm. The difference in zygomatic decreased from(8.5±7.5) mm to(0.7±1.5)mm. The difference in lower orbital point of zygomatic maxillary decreased from(1.9±3.5) mm to(0.6±2.1) mm. The morphology of the affected side and the healthy side was symmetrical. The contour was natural and no postoperative complications occurred. The postoperative satisfaction rate was high. Conclusions:Computer navigation system can solve the problem of limited exposure of lower eyelid-intraoral approach in orbital-zygomatic fibrous dysplasia and significantly improve the accuracy, effectiveness and safety during surgery.

Objectives:To investigate the nursing effect of perioperative enhanced recovery after surgery（ERAS）management model in elderly patients with hip fracture.Methods:A retrospective case-control study was conducted to analyze the clinical data of 94 elderly patients with hip fracture admitted to Second Affiliated Hospital of Soochow University from July 2017 to June 2018，including 24 males and 70 females aged 76-98 years［（83.7±5.4）years］. There were 54 patients with intertrochanteric fracture and 40 patients with femoral neck fracture. Surgical method was proximal femoral nail antirotation（PFNA）fixation or artificial hip arthroplasty. A total of 44 patients were managed by ERAS（enhanced recovery group）and 50 patients by traditional nursing（traditional rehabilitation group）. The off-bed time was compared between the two groups from aspects of different fracture sites，bone mineral density and causes of injury. The visual analogue scale（VAS）was tested preoperatively and at postoperative days 1，3 and 7. The complications were recorded at postoperative 1 month. The activity of daily living（ADL）score was assessed preoperatively and at postoperative 1 week，1 month and 3 months. The Harris hip score was assessed at postoperative 1 week，1 month，3 months and at the last follow-up. The length of hospital stay and death at postoperative 3 months and at the last follow-up were recorded.Results:All patients were followed up for 12-24 months［（17.7±6.2）months］. In enhanced recovery group，the off-bed time of patients with different fracture sites（femoral neck，femoral intertrochanter），bone mineral density（>-2.5 SD，≤-2.5 SD）and causes of injury（falls，traffic accidents and others）were markedly shortened as compared with traditional rehabilitation group（ P<0.01）. There was no significant difference in VAS between the two groups before operation（ P>0.05）. However，the VAS in enhanced recovery group was（3.4±0.9）points，（2.7±0.5）points，（1.7±0.6）points at postoperative days 1，3 and 7，significantly lower than that in traditional rehabilitation group［（4.3±1.1）points，（3.5±0.5）points，（2.7±0.9）points］（ P<0.01）. One month after operation，the incidence of pulmonary infection was 0% in enhanced recovery group and 28%（14/50）in traditional rehabilitation group（ P<0.01）. While there showed no significant differences in incidences of cardiovascular system，nervous system，urinary tract infection，lower limb deep vein thrombosis，impaired liver and kidney function，anemia，electrolyte disorder or hypoalbuminemia between the two groups（ P>0.05）. There was no significant difference in preoperative ADL score between the two groups（ P>0.05）. The ADL score in enhanced recovery group was（37.0±6.6）points，（70.1±8.4）points，（86.2±9.3）points at postoperative 1 week，1 month and 3 months，significantly higher than that in traditional rehabilitation group［（26.5±10.4）points，（50.1±11.4）points，（70.7±9.0）points］（ P<0.01）. The Harris hip score in enhanced recovery group was（80.9±8.6）points at postoperative 1 month，significantly higher than that in traditional rehabilitation group［（71.1±9.2）points］（ P<0.01）. There were no significant differences in Harris hip score between the two groups at postoperative 1 week，3 months and at the last follow-up（ P>0.05）. The length of hospital stay was（4.7±2.4）days in enhanced recovery group，significantly shorter than（7.8±3.9）days in traditional rehabilitation group（ P<0.01）. The enhanced recovery group showed no death within 3 months after operation and 2 deaths［5%（2/44）］at the last follow-up，while the traditional rehabilitation group revealed 4 deaths［8%（4/50）］within 3 months after operation. There was no significant difference in the mortality between the two groups until the last follow-up（ P>0.05）. Conclusion:For elderly patients with hip fracture，perioperative ERAS management model can effectively shorten periods in bed，relieve postoperative pain，reduce incidence of postoperative pulmonary infection，accelerate recovery of hip function，improve quality of life，shorten length of hospitalization and promote early recovery.