In recent years, tumor immunotherapy with immune checkpoint as the target has attracted much attention because of its remarkable efficacy. However, with the application of immune-checkpoint inhibitors (ICIs), more and more immune-related adverse events (irAEs) have been reported. IrAEs impose an additional risk of death on tumor patients treated with ICIs, limiting the widespread use of ICIs. To help patients actively prevent irAEs, biomarkers with the predictive value of irAEs are of great significance. This paper reviews the biomarkers with predictive value for irAEs from the aspects of serology, genetics and microbiology.

OBJECTIVEIn this work, we aim to determine the optimum pH value for the preparation of 3% yttria-stabilized tetragonal zirconia polycrystalline (3Y-TZP)/3%Al₂O₃ and optimum calcination temperature of Al₂O₃ precursor and amorphous boron nitride (BN) for Al₂O₃-BN coating 3Y-TZP powders.

METHODSThe 3Y-TZP/3%Al₂O₃ composite powders were prepared through the heterogeneous precipitation method under different pH values (6.5, 7.5, 8.5, and 9.5) and analyzed through transmission electron microscopy (TEM) to determine the optimum coating morphology. Al₂O₃ precursor, which was prepared under the optimum pH value, was calcined at different temperatures (800, 1 000, 1 200, and 1 400 ℃). The amorphous BN coating 3Y-TZP/3%Al₂O₃ powder was prepared via in situ reaction with boric acid and urea (calcined with N₂ at 850 ℃ for 5 and 3 h and 800 ℃ for 5 and 3 h). TEM, energy dispersive spectrometry (EDS), and X-ray diffraction (XRD) were performed to characterize the results.

RESULTSThe optimum coating morphology was obtained at 8.5 pH. When the Al₂O₃ precursor was calcined at 1 200 ℃ and coated with BN (calcined with N₂ at 800 ℃ for 5 h), the Al-B-O compound was less, and t-ZrO₂ was more represented.

CONCLUSIONSThe optimum pH value for 3Y-TZP/3%Al₂O₃ composite preparation is 8.5. For the preparation of Al₂O₃-BN coating 3Y-TZP powders, the optimum calcination temperature of the Al₂O₃ precursor and amorphous BN are 1 200 and 800 ℃, respectively.

Objective To research the running status of dual-referral in a township of Dongguan city.Methods Hospitals and community health service centers in C town were selected as the research sites.The dual-referral system implementation situatidn in local area was understood by the questionnaire survey on the patients and medical personnel.Results About 44.4％ of patients understood the dual-referral system in local region.However,82.1％ of patients had no the dual-referral experience.The majority of doctors had the experience of upward referral patients and downward referral patients,but their number only accounted for below 10.0 ％ of diagnosis and treatment patients.When the proportion of community reimbursement increased by 20.0％,for the question of whether or not to go to the community first,57.6 ％ of patients expressed willingness,32.7 ％ of patients expressed unwillingness,and 9.7 ％ of patients expressed no influence on own willingness.Conclusion The understand degree of the patients in C township on dual-referral is in the low side.The links of upward transfer and downward transfer of dual referral are insufficient smooth.

Objective: To investigate the relationship between gastrointestinal disorders (GID) and core symptoms or behavioral problems among the children with autism spectrum disorder (ASD) . Method: Totally 328 children with ASD and 202 normal controls were enrolled in this cross-sectional study from August 2013 to October 2016. The information about the gastrointestinal disorders, behavioral and emotional problems was collected by using questionnaires. Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC) were used to assess the core symptoms of the children with ASD. Neurodevelopmental status was evaluated with Gesell Developmental Scale (GDS). These variables were analyzed by using student's t-test and chi-square test. Result: The prevalence of GID was significantly higher in the children with ASD than in the normally developing children (49.4% (162/328) vs.25.7% (52/202), χ²=29.039, P=0.000), especially the symptoms of constipation (33.2% (109/328) vs. 13.9% (28/202)), diarrhea (9.5%(31/328) vs. 1.5% (3/202)), nausea and vomiting (9.5% (31/328) vs. 3.5% (7/202)), and foul defecation (16.5% (54/328) vs. 5.0% (10/202)) (all P<0.05). Among the ASD children, the prevalence of GID was similar between male and female (46.7% (133/285) vs. 46.5%(20/43), χ²=0.006, P=0.938), as well as among all age groups (χ²=1.907, P=0.862). There was no significant difference in scores of GDS in the ASD children with or without GID (all P>0.05). Compared with ASD children without GID (n=166), the ASD children with GID (n=162) got higher scores in the "Body and Object Use" of ABC scale ( (16.4±9.3) vs. (12.3±6.7) scores, t=2.258, P=0.028), and had more emotional problems (63.6% (103/162) vs. 49.4% (82/166), χ²=6.707, P=0.010). Moreover, the score of behavior problems questionnaire was higher in the ASD children with GID ( (35.3±16.8) vs. (16.1±13.6) scores, t=5.748, P=0.000). Conclusion Children with ASD have higher risk of GID than the normal developing children. While the stereotyped behaviors, problem behaviors and emotional problems are severer in the ASD children with GID. Hence, it is important to provide comprehensive treatment and management for these groups of children.

Objective:To evaluate the effect of verbascoside on cold ischemia-reperfusion injury following heterotopic heart transplantation in mice and the relationship with nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) signaling pathway.Methods:This experiment was performed in two parts. Part Ⅰ animal experiment Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 24-28 g, were divided into 3 groups ( n=6 each) by the random number table method: control group (C group), cold ischemia-reperfusion (I/R) group (I/R group) and cold I/R + verbascoside group (I/R+ VB group). Cold I/R injury model of mouse heart transplantation was prepared by neck heterotopic heart transplantation using the modified non-suture cuff technique. The donor heart in group C was immediately transplanted to the recipient after removal, while the donor heart in group I/R was stored in the 4 ℃ University of Wisconsin solution for 8 h before transplantation to the recipient, and verbascoside 20 mg/kg was intraperitoneally injected at 3 days before surgery in donor and recipient mice in I/R+ VB group. At the end of reperfusion, the myocardial tissue of the transplanted heart was obtained after assessing the beating score for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity by enzyme-linked immunosorbent assay. Part of the donor myocardium was taken for examination of the pathological results. The expression of NF-κB, p-NF-κB, NOD-like receptor protein 3 (NLRP3), ACS and caspase-1 was detected by Western blot. The expression of IL-1β, TNF-α and IL-6 mRNA was detected by real-time polymerase chain reaction. Part Ⅱ cell experiment Rat cardiomyocyte H9c2 cold hypoxia-reoxygenation model was developed, and the cells were divided into 3 groups ( n=24 each) by the random number table method: control group (C group), cold hypoxia-reoxygenation group (H/R group), and cold hypoxia-reoxygenation+ verbascoside group (H/R+ VB group). The cells were exposed to hypoxia for 18 h at 10 ℃ followed by restoration of reoxygenation for 24 h at 37 ℃ to develop the cold hypoxia-reoxygenation model. The cell viability and LDH activity were determined. The expression of NF-κB and NLRP3 was detected by Western blot, and the expression of phosphorylated NF-κB (p-NF-κB) was detected by immunofluorescence staining. Results:Part Ⅰanimal experiment Compared with C group, the MDA content was significantly increased, the beating score of grafts and SOD activity were decreased, and the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and myocardial histopathological injury was aggravated in I/R group. Compared with I/R group, the content of MDA was significantly decreased, the beating score of grafts and SOD activity were increased, the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the myocardial histopathological injury was alleviated in I/R+ VB group. Part Ⅱ cell experiment Compared with C group, the cell viability was significantly decreased, the activity of LDH was increased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was up-regulated in H/R group ( P<0.05). Compared with H/R group, the cell viability was significantly increased, the activity of LDH was decreased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was down-regulated in H/R+ VB group ( P<0.05). Conclusions:Verbascoside can alleviate cold I/R injury following heterotopic heart transplantation in mice, and the mechanism may be related to inhibition of activation of NF-κB/NLRP3 signaling pathway.

Coculture between mesenchymal stem cells (MSCs) and chondrocytes has significant implications in cartilage regeneration. However, a conclusive understanding remains elusive. Previously, we reported that rabbit bone marrow-derived MSCs (rbBMSCs) could downregulate the differentiated phenotype of rabbit articular chondrocytes (rbACs) in a non-contact coculture system for the first time. In the present study, a systemic investigation was performed to understand the biological characteristics of chondrocytes in coculture with MSCs. Firstly, cells (MSCs and chondrocytes) from different origins were cocultured in transwell system. Different chondrocytes, when cocultured with different MSCs respectively, consistently demonstrated stimulated proliferation, transformed morphology and declined glycosaminoglycan secretion of chondrocytes. Next, cell surface molecules and the global gene expression of rbACs were characterized. It was found that cocultured rbACs showed a distinct surface molecule profile and global gene expression compared to both dedifferentiated rbACs and rbBMSCs. In the end, cocultured rbACs were passaged and induced to undergo the chondrogenic redifferentiation. Better growth and chondrogenesis ability were confirmed compared with control cells without coculture. Together, chondrocytes display comprehensive changes in coculture with MSCs and the cocultured rbACs are beneficial for cartilage repair.
Cartilage ; Chondrocytes ; Chondrogenesis ; Coculture Techniques ; Gene Expression ; Mesenchymal Stromal Cells ; Phenotype ; Population Characteristics ; Regeneration

Objective: Attentional biases toward emotional scenes may represent vulnerability and maintenance factors in depression. Antidepressant therapy may improve cognitive function and reduce depression, and is considered as the mechanism of action of antidepressants. Therefore, we conducted an eye-tracking test to examine whether selective serotonin re-uptake inhibitor (SSRI) antidepressants can reduce negative attentional biases and elicit clinical responses in depression. Methods: Twenty first-episode depressive patients freely viewed three types of pictures that depicted different emotional scenes (i.e., positive-control, neutral-control, and negative-control) for 4,000 ms while their eye movements were monitored. The attentional bias to different emotional scenes was assessed before and after eight weeks of SSRI treatment using the eye-tracking method. The control group included a group of healthy individuals. Results: The results revealed that first-episode depressive patients oriented their gaze more frequently to negative images and less to happy images, compared to controls. Importantly, the attentional bias in depressive patients was regulated after eight weeks of SSRI treatment. Patients showed an increased tendency to fixate on positive images and a decreased tendency to focus on negative images. Conclusion This suggests that SSRI antidepressants decrease vulnerability to negative images, while having an effect on attention in respect to positive images.

BACKGROUND:Some patients with cervical spondylosis have not been fully corrected sagittal position balance after cervical surgery,and this continuous sagittal position imbalance may be an important reason for the poor long-term clinical outcome of patients. OBJECTIVE:To analyze the correlation between the cervical sagittal position balance parameters and their changes and the clinical efficacy of patients in the unbalanced state after anterior cervical decompression and fusion and to explore the necessity of surgical correction of sagittal balance in order to improve the clinical effect in the later stage. METHODS:A retrospective analysis was performed on 125 patients with cervical spondylosis who underwent anterior cervical decompression and fusion in the Department of Spinal Surgery of Affiliated Hospital of Southwest Medical University from July 2019 to July 2022.Follow-up patients had good postoperative recovery(neck disability index score less than 10%one week after surgery)and had complete follow-up data.According to the axial vertical distance(C2-7 SVA)in sagittal position one week after surgery,patients were divided into type I imbalance group(C2-7 SVA loss≤5 mm,n=27),type Ⅱ imbalance group(C2-7 SVA loss>5 mm,and≤10 mm,n=19),and type Ⅲ imbalance group(C2-7 SVA loss>10 mm,n=12),and non-unbalanced group(C2-7 SVA in the normal range,n=67).The changes of visual analog scale score and neck disability index were compared among groups postoperatively and the last follow-up,as well as the changes of imaging sagittal balance parameters C2-7 cobb angle,C2-7 SVA value,neck inclination angle,T1 inclination angle,and thoracic entrance angle.The correlation between the late clinical effect and postoperative cervical sagittal disequilibrium was explored. RESULTS AND CONCLUSION:(1)There was no statistical difference in general data among the four groups(P>0.05).All patients underwent successful surgery without serious complications and postoperative wound infection.The follow-up time was more than 1 year.(2)There was no significant difference in preoperative symptom score and clinical efficacy one week after surgery(P>0.05).At the last follow-up,pain visual analog scale score,neck disability index and C2-7 SVA were lower than those before surgery but higher than those one week after surgery(P<0.05).C2-7 cobb angle was increased compared with those before operation(P<0.05).T1 inclination angle was decreased compared with those before operation(P<0.05).(3)Pearson correlation test showed that the change of neck disability index was positively correlated with the change of C2-7 SVA(P<0.05).(4)It is indicated that anterior cervical decompression and fusion is effective in the treatment of cervical spondylosis,and can effectively relieve the symptoms of patients.Patients with more severe cervical sagittal disequilibrium after surgery had worse curative effect in the later period.Continuous sagittal disequilibrium in patients with cervical spondylosis after surgery is an important cause of poor curative effect in the later stage.Clinicians should pay more attention to the correction of cervical sagittal balance before and during surgery,formulate surgical strategies and plans according to sagittal balance parameters before surgery,and correct C2-7 SVA intraoperatively to the normal range.

Objective:To investigate the effect of smart air cell mattresses on sleep quality.Methods:Twenty healthy young people were enrolled as subjects, and each subject underwent a four-night polysomnographic monitoring experiment, including two nights each on a smart air cell mattress and a general mattress. The differences in sleep quality were compared by self-assessment of sleep quality, objective sleep indicators, and electroencephalogram (EEG) spectral analysis.Results:In the comparison between the smart air cell mattress and the general mattress, the differences in self-assessment of sleep quality and objective sleep indicators were not statistically significant (all P > 0.05), but the smart air cell mattress had a slight overall advantage. The relative power of EEG in the low-frequency band and the relative power of EEG in the high-frequency band were higher in the subjects with the smart air cell mattress. Conclusions:For the healthy young population, the smart air cell mattress can positively influence sleep quality to some extent, and the change in EEG relative power indicates an increase in sleep depth.

Erectile dysfunction (ED) is a highly prevalent health problem with considerable impact on the quality of men and their partners.There are many drawbacks in the existing ED treatment.Stem cells have the function of self-renewal and differentiation into various cell types.Gene therapy mainly focuses on the regulation of various transmitters and enzymes in nitricoxide synthase/cyclic guanosine monophosphate (NOS/c GMP) pathway,growth factors,peptides and channel proteins,which make them have broad application prospects in the field of ED treatment.In recent years,stem cell and gene therapy of ED have achieved initial results.This article aims to review the latest research progress in this field.