Mitochondria play a crucial role as organelles, managing several physiological processes such as redox balance, cell metabolism, and energy synthesis. Initially, the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria. Recent scholarly works, however, suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer. This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms. Specifically, we review the role of mitochondria transfer in regulating cellular metabolism restoration, excess reactive oxygen species (ROS) generation, proliferation, invasion, metastasis, mitophagy activation, mitochondrial DNA (mtDNA) inheritance, immune system modulation and therapeutic resistance in cancer. Additionally, we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.

ObjectiveTo observe the clinical efficacy and safety of Shugan Bushen Yulin Decoction （疏肝补肾毓麟汤， SBYD） in the treatment of asthenospermia and infertility with liver constraint and kidney deficiency. MethodsA multicenter， randomized， controlled clinical study was conducted in three hospitals in central China. Totally 95 patients with asthenospermia and infertility were controlled. According to random number table， the patients were divided into treatment group （47 cases） and control group （48 cases）. The control group was given vitamin E soft capsules （100 mg per time， twice daily） orally， and the treatment group was given SBYD （one dose daily， 30 min after breakfast and dinner， about 200 ml each time） orally. The course of treatment was 12 weeks in both groups. After the treatment， the sperm concentration， percentage of forward motile sperm （PR）， and percentage of total sperm activity， that is PR + percentage of non-progressively motile sperm （NP） were compared between groups， and the clinical efficacy was judged. Traditional Chinese medicine （TCM） syndrome score （inlcuding 6 single symptom scores and total symptoms score） and 21-item depression， anxiety， and stress scale （DASS-21） scores （including depression， anxiety and stress scores） were compared between the two groups before and after treatment. The patients were followed up for 6 months， and the pregnancy status of spouse between groups was compared. The occurrence of adverse events and vital signs during the trial were recorded for safety assessment. ResultsTwo cases in the treatment group and three cases in the control group dropped out. Finally， 45 cases in each group were included in the statistical analysis. The total effective rate was 86.67% （39/45） in the treatment group， significantly higher than 73.74% （33/45） in the control group （P＜0.05）. After treatment， PR and PR + NP significantly increased in both groups， and were much higher in the treatment group than in the control group （P＜0.05）. The scores of lumbar and knee soreness， emotional disturbance， cold sperm， chest and rib-side and lesser abdomen distension and pain， frequent sighing， and the total TCM syndrome score in the treatment group decreased after treatment （P＜0.05）； and except for cold sperm， the scores of other symptoms mentioned above as well as the total TCM syndrome score in the treatment group were lower than those in the control group （P＜0.05）. The scores of depression， anxiety and stress of DASS-21 in the treatment group decreased after treatment， and were lower than those in the control group （P＜0.05）. After 6 months of follow-up， the spouses of 5 patients in the treatment group and 3 patients in the control group got pregnant （P＞0.05）. No adverse events occurred in both groups during the treatment， and their vital signs were stable. ConclusionSBYD can obviously improve sperm vitality and effectively improve the clinical symptoms， anxiety and depression， and is safe in treating asthenospermia and infertility with liver constraint and kidney deficiency.

Objective:To investigate the clinicopathological features and molecular genetic characteristics of esophageal carcinoma with ductal differentiation, and to summarize the experiences in its diagnosis and treatment.Methods:A total of 17 cases of esophageal carcinoma with ductal differentiation diagnosed in Ningbo Clinical Pathological Diagnosis Center, Ningbo, China from June 2011 to December 2022 were collected. The clinical information and pathological diagnosis was reviewed. The tumor histological features and immunohistochemical results were analyzed. The next-generation sequencing was performed to detect and analyze the gene mutations in tumor samples.Results:The 17 patients included in this study were 54-77 years old, with a median age of 66 years. There were 16 males and 1 female. Among them, 9 cases were mainly carcinoma with ductal differentiation. The squamous epithelium on the tumor′s surface was accompanied by high-grade intraepithelial neoplasia. The tumor and atypical squamous epithelium were transitional, and the focus was accompanied by various proportions of squamous cell carcinoma component (less than 10%). The other 8 cases were mostly squamous cell carcinoma, basaloid squamous cell carcinoma or sarcomatoid carcinoma with various degrees of tumor specific differentiation and focal area of carcinoma with ductal differentiation (less than 10%). The tumor cells in the area with ductal differentiation were mainly arranged in small tubes, while the tubes showed a double-layer structure, including the inner cells and outer cells of the lumen. Immunohistochemical results showed that the outer cells of the tumorous tubules expressed p63, p40, CK5/6 and CK34βE12, while the inner cells expressed CK7. Compared with esophageal squamous cell carcinoma reported in the literature, the frequency of gene mutations such as MYC ( P=0.002), TP63 ( P=0.002), CDKN1C ( P=0.002) and NFE2L2 ( P=0.045) was significantly lower in this group of cases. At the signaling pathway level, the mutation frequency of NOTCH signaling pathway ( P=0.041) was significantly higher, while the mutation frequencies of NRF2 pathway ( P=0.013) and PI3K pathway ( P=0.009) were significantly lower than that of esophageal squamous cell carcinoma. Conclusion:Esophageal carcinoma with ductal differentiation is a type of esophageal carcinoma with unique morphology, and its molecular changes are also significantly different from those of conventional esophageal squamous cell carcinoma.

BACKGROUND:The assessment of asymmetric gait quality plays a pivotal role in guiding rehabilitation training;however,the link between gait quality and kinematic-kinetic gait parameters remains ambiguous. OBJECTIVE:To formulate a machine-learning model for evaluating gait quality based on gait parameters,identify factors sensitive to gait quality from asymmetric gait parameters,investigate the relationship between gait indicators and gait quality,and provide guidance for asymmetric gait training and rehabilitation. METHODS:An asymmetric gait database was established through the creation of asymmetric conditions.Kinematic and kinetic data were collected from 8 young and 8 elderly subjects(all male,right dominant population)during gait tests.Gait quality for each test data set was assessed using symmetry indices,resulting in the creation of a gait parameter-gait quality dataset.Utilizing the Random Forest algorithm,a gait quality evaluation model was developed and key quality parameter factors were identified through differential analysis.This model was iteratively refined.The model's performance was evaluated through 10-fold cross-validation,and its effectiveness was verified using the cross-validation dataset. RESULTS AND CONCLUSION:(1)A gradient test was designed to categorize gait quality into optimal,suboptimal,intermediate,and poor groups,with 759,329,133,and 125 instances,respectively.(2)The application of the Random Forest algorithm in gait quality assessment was explored.A relationship model was established between gait indicators and gait quality,yielding a predictive model accuracy of 95.99%.(3)The 13 main parameters significantly influencing asymmetric gait quality were identified through the Random Forest model's feature importance ranking.(4)An analysis of gait quality sensitivity factors using the 13 important parameters led to the identification of five key sensitivity indexes.The Random Forest model utilizing these sensitivity factors achieved a predictive accuracy of 94.20%.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective:To explore the mechanism of peritoneal dialysis solution (PDS)-induced peritoneal microinflammation through activation of ceramide (CER) in peritoneal dialysis model mice.Methods:Thirty 5-week-old male C57BL/6 mice weighing about 22 g were used to set up peritoneal dialysis models, and then were randomly divided into 4 groups: sham operation group (1.5 ml sterilized water, n=7), high glucose-PDS group (1.5 ml 4.25% PDS, n=8), high glucose-PDS+ acid sphingomyelinase (ASMase) inhibitor desipramine (DES) group (1.5 ml sterilized water+10 mg/kg DES, n=8), high glucose-PDS+Src kinase inhibitor PP2 group (1.5 ml sterilized water +1 mg/kg PP2, n=7), with intraperitoneal injection once a day. After 28 days, the mice were sacrificed to retain peritoneal tissues. HE staining and Masson staining were used to observe the histological changes of peritoneum. Immunohistochemistry was used to detect the Toll-like receptor 4 (TLR4) and macrophages. High performance liquid chromatography, liquid chromatography/mass spectrometry and immunofluorescence were used to detect the expression of ASMase and CER. Real-time quantitative PCR was used to detect the mRNA levels of c-Src, p-Src, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Western blotting was used to detect the protein levels of c-Src, and p-Src. Enzyme-linked immunosorbent assay was used to detect the serum C reactive protein (CRP), IL-6 and TNF-α. Results:(1) High glucose-PDS led to peritoneal hyperplasia, collagen deposition and fibrosis in the peritoneal dialysis mice, indicating successful modeling. Compared with high glucose-PDS group, peritoneal hyperplasia, collagen deposition and fibrosis of mice treated with DES and PP2 were significantly improved (all P<0.05). (2) Compared with sham operation group, ASMase activation and CER level of peritoneal tissues were significantly higher in high glucose-PDS group, and DES could significantly inhibit activated ASMase and increased CER expression caused by high glucose-PDS (both P<0.05). PP2 had no significant effect on ASMase activation and CER level (both P>0.05). (3) Compared with sham operation group, there were more TLR4 and macrophage positive staining cells in peritoneal tissues in high glucose-PDS group, and the mRNA expression levels of IL-6 and TNF-α in peritoneal tissues and serum CRP, IL-6 and TNF-α were higher (all P<0.05). DES and PP2 could significantly inhibit the increased TLR4, macrophages and related inflammatory factors induced by high glucose-PDS (all P<0.05). (4) Compared with sham operation group, c-Src and p-Src mRNA and protein expression levels of peritoneal tissues in high glucose-PDS group were significantly higher (all P<0.05). PP2 significantly inhibited the increased p-Src mRNA and protein levels caused by high glucose-PDS (both P<0.05), but had no significant effect on the mRNA and protein expression levels of c-Src (both P>0.05). DES had no significant effect on the mRNA and protein expression levels of c-Src and p-Src (all P>0.05). Conclusions:High glucose-PDS may enhance the expression of CER through stimulating the activity of ASMase, phosphorylate Src, activate TLR4 and induce inflammatory damage of peritoneum in peritoneal dialysis model mice.

Objective:To establish a scoring system for preoperative prediction of the malignant potential of gastric stromal tumors based on gastroscopic and endoscopic ultrasound features, along with validation.Methods:A total of 286 patients who were treated in Jiangsu Province Hospital of Chinese Medicine from January 1, 2017 to December 31, 2023 and diagnosed as having gastric stromal tumors by postoperative pathology were enrolled in the modeling group. According to National Institutes of Health classification system, 227 very-low/low-risk patients were classified into the low malignant potential (LMP) group, and the 59 intermediate/high-risk patients into the high malignant potential (HMP) group. LASSO regression analysis was performed to identify predictive factors for HMP gastric stromal tumors, and a nomogram prediction model was developed. Internal validation using the Bootstrap method was performed on the modeling group, and external validation was performed on data from 85 patients who were treated and diagnosed as having gastric stromal tumors by postoperative pathology in Taizhou People's Hospital from January 1, 2021 to December 31, 2023. The receiver operator characteristic (ROC) curves, calibration curves, and decision curve analyses were employed in both the modeling and external validation groups.Results:Tumor size (coef=0.755), tumor shape (coef=0.015), tumor location (coef=0.008), growth pattern (coef=-0.026), cystic change (coef=0.685), and surface unceration change (coef=-0.545) were the independent predictive factors for HMP gastric stromal tumors. The nomogram-based prediction model constructed using these factors achieved an area under the ROC curve of 0.959 (95% CI: 0.898-0.903) in the modeling group and 0.959 (95% CI: 0.857-1.000) in the external validation group. The model demonstrated good accuracy (0.917) and a Kappa value of 0.737 in internal validation. Calibration curve and decision curve analyses indicated strong calibration and high net benefit in both the modeling and the external validation groups. Conclusion:Tumor size, tumor shape, tumor location, growth pattern, cystic change, and surface ulceration change are independent predictive factors for HMP gastric stromal tumors. The nomogram model developed based on these factors offers effective and convenient visualization for clinicians to predict the malignant potential of gastric stromal tumors preoperatively.

Objective:To investigate the effect of separation exercise training of upper limb robot in improving upper limb motor function of stroke patients,and to explore the underlying mechanism by transcranial magnetic stimu-lation motor-evoked potential(MEP)evoked potentials. Method:Stroke patients were randomly divided into the experimental group(n=21)and the control group(n=23).The experimental group was trained with a fixed trajectories(the separation movement of elbow flexion-extension and shoulder adduction-abduction),while the control group underwent upper limb robot training with random movement trajectories(a compound action that can reach for objects).Both groups received robot train-ing once a day,20min/time,5 times/week for 3 weeks.The Fugl-Meyer assessment of upper extremity(FMA-UE)and modified Barthel index(modified Barthel index,MBI)were used to evaluate motor function.The la-tency period and central motor conduction time(CMCT)of MEP were detected before and after treatment. Result:After 3 weeks of treatment,the FMA-UE,MBI and MEP were improved compared with before treat-ment in the experimental group(P＜0.05),There was no significant difference between the FMA-UE,MBI and MEP of the control group and that before treatment(P＞0.05);There were no significant differences in in FMA-UE,MBI and MEP between-group comparisons after 3 weeks of treatment. Conclusion:The separation exercise training of the upper limb robot can improve the upper limb motor func-tion and enhance daily living activities in stroke patients,which may be related to enhanced remodeling of brain function in stroke patients.

Bacteria have posed a threat to human health,and the emergence of super bacteria has made it more difficult to cure bacterial infections in clinical practice.Currently,vaccines are one of the effective means of preventing bacterial infections.With the rapid development of cutting-edge technologies in recent years in such disciplines as biology,medicine,and materials science,various innovative strategies have been provided for vaccine research and preparation.This article summarizes the status quo and prospects of innovative vaccines for treating bacterial infections in recent years,including subunit vaccines,mRNA vaccines and attenuated live vaccine in the hopes of providing data for subsequent development and research of bacterial vaccines.

Objective:To explore the risk factors of oral-mucosal pressure injury (OMPI) in patients with tracheal intubation in ICU and to establish a nomogram model.Methods:Using the convenient sampling method, a total of 640 patients with oral tracheal intubation admitted to ICU of the First Affiliated Hospital of Xinjiang Medical University from January to May 2023 were selected as the research objects. They were divided into the occurrence group ( n=286) and the non-occurrence group ( n=354) according to whether OMPI occurred or not. Binomial Logistic regression analysis was used to explore the risk factors for OMPI in patients with tracheal intubation in ICU. A risk nomogram model was created based on independent risk factors, and internal verification was conducted by Bootstrap repeated sampling method. Results:OMPI occurred in 286 of 640 ICU patients with tracheal intubation. Binomial Logistic regression analysis showed that high APACHEⅡ score, modified Beck oral score greater than or equal to 11 points, use of sedative drugs, prone ventilation, long retention time of tracheal catheter, low oxygenation index less than 200 mmHg (1 mmHg=0.133 kPa) and tracheal catheter fixation frequency of 1 time /24 h were the risk factors for OMPI in patients with tracheal intubation in ICU ( P<0.05). A risk nomogram model for OMPI in patients with tracheal intubation in ICU was established based on independent risk factors. The results showed that the predictive performance (area under the receiver operating characteristic curve of subjects was 0.918, 95% confidence interval was 0.897 to 0.938) and calibration (χ 2 value of 4.647, P=0.795) of the risk nomogram model for OMPI in patients with tracheal intubation in ICU were good. When the threshold probability was 0 to 1, the decision curve showed that the model had good clinical effectiveness. Conclusions:The OMPI risk nomogram model of tracheal intubation patients in ICU established in this study has good calibration and differentiation, which can be used as an effective tool for screening high-risk patients.