Objective:To investigate the role of Pink1/Parkin-induced mitophagy in acute lung injury of exertional heat stroke rats.Methods:Sixty SD rats were randomly divided into four groups, including normal group (CON group), normal Parkin overexpression group (CON+Parkin group), heat stroke group (EHS group) and heat stroke Parkin overexpression group (EHS+Parkin group), with fifteen rats in each group. The rat model of exertional heat stroke was established and the survival curve was drawn. Pulmonary coefficient and pulmonary capillary permeability were detected. HE staining was used to observe the pathological changes of lung tissue. ELISA was used to detect the contents of IL-6, IL-1β, TNF-α and ROS in lung tissue; immunohistochemistry was used to observe apoptosis in lung tissue; Western blot was used to determine the expression of Pink1, Parkin, P62 and LC3 in rat lung tissue, and the LC3II/LC3I ratio was calculated. Single factor multi-level group comparison was performed by single factor analysis of variance, SNK-q method was used to further pairwise comparison between groups.Results:Compared with the normal group, the survival rate of EHS group was decreased ( P<0.001), lung coefficient and pulmonary vascular permeability were increased [(4.39±0.42), (33.38±8.29) μg/g, P<0.05)], lung tissue was exudative and solid, the levels of inflammatory factors IL-6, IL-1β, TNF-α and ROS were significantly increased[(34.31±5.34) pg/mL, (34.03±4.78) pg/mL, (91.64±8.16) pg/mL, (259.01±89.17) U/mg, P<0.05)], and apoptosis was increased. Western and immunohistochemistry results showed that the expressions of Pink1 and Parkin were decreased, co-location of Pink1and Parkin was attenuated, LC3II/LC3I were decreased, and P62 expression was increased. Compared with the EHS group, the survival rate of EHS+Parkin group was significantly increased ( P<0.05), lung coefficient and pulmonary vascular permeability were decreased [(3.83±0.62), (22.49±7.90) μg/g, P<0.05)], exudation and consolidation and other pathological changes were significantly reduced, and the levels of the above inflammatory factors and ROS were significantly decreased [(14.09±3.24) pg/mL, (26.94±2.11) pg/mL、(63.35±11.62) pg/mL, (161.13±26.31) U/mg, P<0.05]. Lung tissue apoptosis was reduced. The co-location of Pink1and Parkin、Parkin expression and LC3II/LC3I ratio were increased ( P<0.05), P62 expression was decreased( P<0.05), while Pink1 expression was not significant different (q=0.75). There was no difference between normal group and normal Parkin overexpression group (q=0.95). Conclusion:Activation of Pink1/Parkin-induced mitophagy can alleviate the acute lung injury in exertional heat stroke rats.

Objective:To explore the properties of gelatin-polyethylene glycol hydrogel loaded with silver nanoparticle (AgNP) Chlorella (hereinafter referred to as the composite hydrogel) and its effects on healing of infected full-thickness skin defect wounds in mice. Methods:The research was an experimental research. The simple gelatin-polyethylene glycol hydrogel (hereinafter referred to as the simple hydrogel) and the composite hydrogel were prepared, and the appearance and injectability of the two hydrogels were observed at 55 and 37 ℃, and under the irradiation of 808 nm near-infrared light, respectively. An electronic universal testing machine was employed to assess the tensile and compressive stress-strain properties of both types of hydrogels at room temperature. Additionally, the cyclic compressive stress-strain properties of the composite hydrogel were examined at 80% of the maximum compressive stress. Staphylococcus aureus or Escherichia coli solution was added to phosphate buffer solution (PBS), simple hydrogel, and composite hydrogel, respectively. The part of composite hydrogel containing Staphylococcus aureus or Escherichia coli solution was irradiated with near-infrared light for 5 minutes. After each sample was incubated for 6 h, the dilution plating method was used to detect and calculate the mortality rates of the two bacteria at 24 h of culture ( n=5). The discarded foreskin tissue was taken from a 6-year-old healthy boy admitted to the Department of Urology of the First Affiliated Hospital of Naval Medical University for circumcision. Primary human fibroblasts (HFbs) were isolated using the enzyme extraction method, routinely cultured to the 3 rd to 6 th passages for subsequent cellular experiments. Composite hydrogel extracts with final mass concentrations of 100.0, 50.0, 25.0, 12.5, and 0 mg/mL were respectively prepared and used to culture HFbs, and the cell proliferation after 24 h of culture was detected using a cell counting kit 8 ( n=3). A total of twenty 6-8 weeks old C57BL/6J female mice were utilized, and a full-thickness skin defect was surgically created on the back of each mouse. The wounds were infected with Staphylococcus aureus solution. The infected mice were divided into blank control group, simple hydrogel group, composite hydrogel group, and combined treatment group according to the random number table, and the wounds were treated with PBS, simple hydrogel, composite hydrogel, and composite hydrogel+light irradiation (under the irradiation of 808 nm near-infrared light for 5 min), respectively, with 5 mice in each group. On post injury day (PID) 0 (immediately after the first wound treatment), 3, 7, and 14, an overall assessment of wound exudation and healing were conducted, and the wound healing rates on PID 7 and 14 were calculated ( n=5). On PID 14, hematoxylin-eosin staining was performed to observe histopathological changes in the mouse wound. Results:Both simple hydrogel and composite hydrogel were in a solution state at 55 ℃ and transition to a gel state when cooling to 37 ℃. After the two hydrogels were irradiated by near-infrared light, only the composite hydrogel reheated up and returned to the solution state again with injectability. The maximum tensile stress of the composite hydrogel was up to 301.42 kPa, with a corresponding strain of 87.19%; the maximum compressive stress was up to 413.79 kPa, with a corresponding strain of 91.67%, which was similar to the tensile and compressive properties of the simple hydrogel. After 10 compression cycles, the maximum compressive stress of the composite hydrogel still reached 84.1% of the first compressive stress. After 24 h of culture, the mortality rate of Staphylococcus aureus treated with simple hydrogel was significantly higher than that treated with PBS ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel alone were significantly higher than those treated with simple hydrogel ( P<0.05); the mortality rates of Escherichia coli and Staphylococcus aureus treated with composite hydrogel+light irradiation were significantly higher than those treated with composite hydrogel alone ( P<0.05). After 24 h of culture, compared with that cultured in composite hydrogel immersion solution with final mass concentration of 0 mg/mL, the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentrations of 25.0 and 50.0 mg/mL was significantly enhanced ( P<0.05), while the proliferation activity of HFbs cultured in composite hydrogel immersion solution with final mass concentration of 100 mg/mL was significantly decreased ( P<0.05). On PID 0 and 3, more purulent secretions were seen in the wounds of mice in blank control group and simple hydrogel group, while only a small amount of exudate was observed in the wounds of mice in composite hydrogel group, and no obvious infection was observed in the wounds of mice in combined treatment group. On PID 7 and 14, the wound healing rates of mice in simple hydrogel group were significantly higher than those in blank control group ( P<0.05); the wound healing rates of mice in composite hydrogel group were significantly higher than those in simple hydrogel group ( P<0.05); the wound healing rates in combined treatment group were significantly higher than those in composite hydrogel group ( P<0.05). On PID 14, the wounds of mice in blank control group exhibited a high infiltration of inflammatory cells with no new epithelial layer observed; the wounds of mice in simple hydrogel group displayed a short length of newly formed epithelium with a small amount of inflammatory cells; the wounds of mice in composite hydrogel group exhibited continuous formation of new epithelium and a large amount of immature granulation tissue; the wounds of mice in combined treatment group showed continuous epithelialization with less immature granulation tissue. Conclusions:The prepared composite hydrogel exhibits excellent thermosensitivity, photothermal properties, and injectability, as well as excellent mechanical properties, antibacterial properties, and biocompatibility, and can promote the healing of infected full-thickness skin defect wounds in mice.

Objective To construct a radiomic model based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI ) for preoperative prediction of hepatocellular carcinoma (HCC ) differentiation and validate its clinical value.Methods Clinical and imaging data of 187 HCC patients who received surgical treatment in the Third Affiliated Hospital of Chongqing Medical University from June 2018 to January 2024 were collected and retrospectively analyzed.According to the postoperative pathological results,they were divided into low-differentiation group (n=58)and non-low-differentiation group (n=129),andrandomly divided into the training group (n=149)and the validation group (n=38)with the ratio of 8∶2. Univariate analysis was used to assess the clinical indicators related to HCC differentiation,and then a clinical model was constructed. Pyramidimics software was used to extract the radiomic features of IVIM-DWI functional images,and minimum absolute contraction and selection operator logistic regression algorithm were employed to screen those highly correlated indicators with HCC differentiation.Support vector machine (SVM),logistic regression (LR)and random forest (RF)algorithms were utilized to construct different image omics models.SVM algorithm was applied to construct the combined imaging omics and clinical model. The internal verification of the model was carried out by using ten-fold cross-validation.Receiver operating characteristic (ROC)curve,area under the curve (AUC),calibration curve,and decision curve analysis (DCA)were used to evaluate the diagnostic value and clinical benefits of clinical model,radiomic model,and their combination.Results A total of 4060 radiological features were extracted,and after feature screening and dimensionality reduction,24 features were finally included to construct the model.Among all models,the predictive performance of the radiomic model and the radiomic-clinical combined model was better than that of the clinical model.In the comparison between the radiomic model constructed by SVM algorithm and the radiomics-clinical combined model,the AUC value was 0.954 (0.908～1.000)for the former model,and was 0.943 (0.905～0.982)for the latter model in the training set,and there was no significant difference between them.In the validation set,the AUC value was 0.807 (0.640～0.975 )and 0.876 (0.743～1.000),respectively,with statistical difference between the 2 models (P<0.05).Calibration curve analysis showed that the radiomic model and the radiomics-clinical combined model had good goodness of fit.DCA indicated that the net benefit was higher and the threshold probability range was larger in both the radiomic model and the radiomics-clinical combined model,and the net benefit of the combined model was larger. Conclusion Both the radiomic model and the combined radiomics-clinical model constructed on the basis of IVIM-DWI functional images can better predict the severity of HCC differentiation before surgery.

Cervical lymph node metastasis in thyroid cancer is closely related to the disease recurrence and prognosis of patients. Accurate judgment of lymph node metastasis is vital for tumor stage and treatment in patients with thyroid cancer, which can effectively improve the prognosis of patients. However, preoperative detection of cervical lymph node metastasis is the key points and difficulties in individualized treatment of thyroid cancer. Currently, fine needle aspiration washout fluid thyroglobulin is often used to assess cervical lymph node metastasis of differentiated thyroid cancer preoperatively, and it has a higher diagnostic efficacy. The continuous exploration and application of tumor markers and emerging biomarkers have provided new perspectives for the preoperative diagnosis of lymph node metastasis in thyroid cancer. As a new non-invasive detection technique, liquid biopsy is convenient to obtain samples and has broad clinical application in early diagnosis of cervical lymph node metastasis of thyroid cancer. In addition, the analysis and application of liquid biopsy biomarkers will help the development of clinical diagnosis and treatment strategies, and provide the possibility of early precision therapy for thyroid cancer patients. This review summarizes current research surrounding the molecular markers related to cervical lymph node metastasis of thyroid cancer.

Circular RNA(circRNA)is an emerging class of endogenous non-coding RNA,which is widely expressed in the brain and plays an important role in a variety of biological processes.Research has shown that circRNA plays a key role in physiological and pathological processes of the brain,such as neurodevelopment,synaptic plasticity and neurodegenerative diseases through a variety of mecha-nisms such as adsorption of microRNA,binding to proteins and translation of peptides.In the field of drug addiction,the expression of circRNA is significantly changed in animal models and brains of addicts,and the regulation involves neural adaptation in brain regions that form the reward circuit such as the nucleus accumbens and prefrontal cortex.Additionally,addiction-related circRNAs are closely associated with neurotransmitter systems,signaling pathways,and neuroinflammatory responses,and they influ-ence the formation and maintenance of drug addiction by modulating gene expression networks related to drug addiction.Here,the biogenesis and regulatory mechanism of circRNA as well as its important role in brain function and drug addiction are reviewed in order to provide a new perspective for explora-tions of the pathological mechanism of drug addiction.

Objective:To explore the effect and safety of endoscopic tubular musculoskeletal tumor surgery (ETMS) technology in spinal tumors.Methods:Clinical data were retrospectively collected from 18 spinal tumor patients who were treated with ETMS technology at Tianjin Medical University Cancer Institute and Hospital ( n=16) or the Affiliated Hospital of Qingdao University ( n=2) from November 2022 to December 2023. The total cohort included 11 males and 7 females, with the age at 60.3±8.6 years (range of 41-76). Two cases were diagnosed with benign tumors, four patients were diagnosed with spinal hematologic malignancies while other 12 cases were patients with spinal metastases. After localization under the C-arm X-ray machine, the spinal endoscopic channel is established using dilators. Soft tissue is dissected under endoscopic guidance to create an artificial cavity. Subsequently, the saline medium relied upon by the spinal endoscopic technique is removed, and posterior decompression and tumor curettage are performed using tubular techniques. Frankel grade classification and paraplegia index were used to evaluate the improvement of postoperative function and the VAS score was performed in pain scoring. The surgical complications and tumor evaluation were observed by postoperative outpatient and telephone follow-up. Results:The ETMS technology was successfully completed in all 18 patients with the mean operation time of 240.3±80.2 min. The median of intraoperative bleeding was 200.0(172.5, 350.0) ml and the mean postoperative drainage was 131.4±69.5 ml. The median value of postoperative hospitalization days was 6.0(4.0, 10.25) d. The paraplegia index decreased from 1.5(0, 3.0) preoperatively to 0(0, 1.25) postoperatively ( Z=-2.599, P=0.009). All the patients presented an improvement in Frankel grading after surgery except for one patient (downgrading from grade E to grade D). There was significantly difference in Frankel grading between preoperative and postoperative groups ( Z=2.812, P=0.005). The median value of preoperative VAS score was up to 5.5(4.0, 7.0) while the median value at postoperative, one month after surgery and three months after surgery were 1.5(1.0, 2.25), 1.0(0, 1.0) and 0(0, 1.0), respectively (χ 2=44.641, P<0.001). The 3-month postoperative VAS improvement rate was 91.2% (range 75%-100%). During a mean follow-up period of 7.6±6.2 months, none of the 18 patients presented surgical complications or tumor recurrence at surgical region. Only one patient died at 3.2 months after surgery until the last follow-up due to respiratory failure after lung tumor progression. The mean survival of the total cohort was up to 13.3 [95% CI (11.5, 15.0)] months. The 16 cases with spinal metastases or spinal hematological malignancies had a mean survival of 13.2 [95% CI (11.3, 15.0)] months. Conclusion:The ETMS technology presented good efficacy and safety in treatment of spinal tumors with low blood supply and with diameter less than 5cm.

Objective To comparatively observe the incidence of complications and patency rate within 1 year after implantation of totally implantable venous access port(TIVAP)through internal jugular vein(IJV)between different locations of catheter tip.Methods Data of 2 104 patients with tumors who received TIVAP implantation through IJV were retrospectively analyzed.Patients who underwent TIVAP implantation through the right IJV(group R,n=1 903)were divided into R1(n=376,with catheter tip located at the upper right atrium,i.e.0.5 to 1.0 cm below the cavoatrial junction[CAJ])and R2 subgroups(n=1 527,with catheter tips located between the lower 1/3 of superior vena cava[SVC]and CAJ),while those who underwent TIVAP implantation through the left IJV(group L,n=201)were divided into L1(n=64)and L2 subgroups(n=137),respectively.Patients'basic information,incidence of complication and patency rate of catheter 1 year after TIVAP implantation were collected and compared between subgroups.Results No significant difference of gender,age,clinical diagnosis,tumor stage,nor of incidence of complication including pneumothorax/hemopneumothorax,local skin injury,TIVAP infection,catheter-associated thrombosis,drug extravasation,catheter displacement and arrhythmia was found between subgroups within group R nor L(all P＞0.05).One year after TIVAP implantation,no significant difference of catheter patency rates was found between subgroup R1(94.15%)and R2(93.78%)(χ2=0.069,P=0.793),nor between subgroup L1(98.44%)and L2(89.78%)(Yates'continuity correction χ2=3.563,P=0.059).Conclusion No significant difference of incidence of complications nor catheter patency rate within 1 year after implantation of TIVAP was found between catheter tip location at the upper right atrium or between the lower 1/3 of SVC and CAJ through the right or left IJC.

Objective:To explore the cellular heterogeneity and the differences in branched trajectory of pericytes between keloids and localized scleroderma, and to provide new clues for the pathogenesis and therapeutic targets of the two skin fibrotic diseases.Methods:Single cell transcriptome sequencing (scRNA-seq) data of 3 cases of scleroderma, 4 cases of keloid and their corresponding 4 cases of adjacent normal skin samples were selected from GEO and GSA-Human databases, and the expression matrix of the data was drawn. Seurat 4.3.0 of R (4.2.2) was used to process the t-distributed stochastic neighbor embedding ( t-SNE) visualization map. Monocle 2.24.0 was used to analyze the pseudo-temporal trajectory of pericytes. Results:The unsupervised clustering of keloid and scleroderma skin tissues revealed 19 different cell populations, among which C7 and C11 cells were pericytes, marked by high expression levels of PDGFRB and RGS5 genes, accounting for 7.53% of the total cells. Pericytes can be further divided into 8 subgroups. Pseudo-temporal analysis revealed a branched trajectory with two major branches, that is, cell fate 1 and cell fate 2, which could be further divided into 5 cellular states of pericytes (S1-S5). S4 constituted the most of the prebranch, which represented the cellular state of the initial pericyte phenotype. S5 constituted the most of the cell fate 1 branch, which represented the early differentiation state of the pericyte phenotype. S1, S2, S3 constituted the most of the cell fate 2 branch. S3 represented the intermediate differentiation state of the pericyte phenotype, while S1 and S2 represented the terminal differentiation states of the pericyte phenotype. Compared with the uniform distribution of various differentiation states of pericytes in normal skin, the keloid pericytes mainly distributed in the prebranch (S4), cell fate 1 (S5) and the first half of cell fate 2 (S3), representing cellular states of the initial, early and intermediate phases of the pericyte phenotype. Branched expression analysis modeling revealed the overexpression of SOX4, COL4A1, COL6A3, AHR, CXCL3 and IL1R1 genes, et cetera. On the other hand, the localized scleroderma pericytes mainly distributed in the bottom half of cell fate 2 (S1, S2), representing the final differentiated phase of pericyte phenotype, which overexpressed ACTA2 and MYH11 genes.Conclusion:Pericytes in keloid and scleroderma are heterogenous and have different differentiation trajectories. Pericytes in keloid have stem-like characteristics, and play an important role in the pathologic characteristics of invasiveness and recurrence through high expression of genes related to cell stemness, epithelial-mesenchymal transition, invasiveness, and immune microenvironment regulation. However, pericytes in localized scleroderma may mainly transdifferentiate into myofibroblasts, leading to their fibrotic pathological phenotype.

Objective:To explore the cellular heterogeneity and the differences in branched trajectory of pericytes between keloids and localized scleroderma, and to provide new clues for the pathogenesis and therapeutic targets of the two skin fibrotic diseases.Methods:Single cell transcriptome sequencing (scRNA-seq) data of 3 cases of scleroderma, 4 cases of keloid and their corresponding 4 cases of adjacent normal skin samples were selected from GEO and GSA-Human databases, and the expression matrix of the data was drawn. Seurat 4.3.0 of R (4.2.2) was used to process the t-distributed stochastic neighbor embedding ( t-SNE) visualization map. Monocle 2.24.0 was used to analyze the pseudo-temporal trajectory of pericytes. Results:The unsupervised clustering of keloid and scleroderma skin tissues revealed 19 different cell populations, among which C7 and C11 cells were pericytes, marked by high expression levels of PDGFRB and RGS5 genes, accounting for 7.53% of the total cells. Pericytes can be further divided into 8 subgroups. Pseudo-temporal analysis revealed a branched trajectory with two major branches, that is, cell fate 1 and cell fate 2, which could be further divided into 5 cellular states of pericytes (S1-S5). S4 constituted the most of the prebranch, which represented the cellular state of the initial pericyte phenotype. S5 constituted the most of the cell fate 1 branch, which represented the early differentiation state of the pericyte phenotype. S1, S2, S3 constituted the most of the cell fate 2 branch. S3 represented the intermediate differentiation state of the pericyte phenotype, while S1 and S2 represented the terminal differentiation states of the pericyte phenotype. Compared with the uniform distribution of various differentiation states of pericytes in normal skin, the keloid pericytes mainly distributed in the prebranch (S4), cell fate 1 (S5) and the first half of cell fate 2 (S3), representing cellular states of the initial, early and intermediate phases of the pericyte phenotype. Branched expression analysis modeling revealed the overexpression of SOX4, COL4A1, COL6A3, AHR, CXCL3 and IL1R1 genes, et cetera. On the other hand, the localized scleroderma pericytes mainly distributed in the bottom half of cell fate 2 (S1, S2), representing the final differentiated phase of pericyte phenotype, which overexpressed ACTA2 and MYH11 genes.Conclusion:Pericytes in keloid and scleroderma are heterogenous and have different differentiation trajectories. Pericytes in keloid have stem-like characteristics, and play an important role in the pathologic characteristics of invasiveness and recurrence through high expression of genes related to cell stemness, epithelial-mesenchymal transition, invasiveness, and immune microenvironment regulation. However, pericytes in localized scleroderma may mainly transdifferentiate into myofibroblasts, leading to their fibrotic pathological phenotype.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.