OBJECTIVE: Based on the PTEN-induced hypothetical kinase 1 (PINK1)/Parkin pathway, the effect of acupuncture pretreatment on the expression of mitochondrial autophagy-related proteins in gastrocnemius muscle tissue of rats with exercise-induced muscle damage (EIMD) was observed, and the underlying mechanism of acupuncture pretreatment for the prevention and treatment of EIMD was explored. METHODS: Of 88 SD male rats, aged 6 weeks, 8 rats were randomly selected as a blank group, and the remaining 80 rats were randomized into a model group and an acupuncture pretreatment group, with 40 rats in each group. Either the model group or the acupuncture pretreatment group was subdivided randomly into 5 subgroups with 8 rats in each one according to the time points of sample collection, 0 h, 12 h, 24 h, 48 h and 72 h after modeling. An intermittent downhill running centrifugal exercise was carried out on an animal experimental treadmill to establish the EIMD model in the model group and the acupuncture pretreatment group. The rats in the acupuncture pretreatment group received acupuncture at "Guanyuan" (CV6) and bilateral "Zusanli" (ST36), once a day for 20 min each time, for 7 consecutive days before EIMD model preparation. Transmission electron microscopy was used to observe the ultrastructure of gastrocnemius muscle tissue in each group. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) in serum were detected by ELISA. Western blot was used to detect the protein expression of PINK1, Parkin, sequestosome 1 (p62) and microtubule-associated protein light chain 3B (LC3B) in rat gastrocnemius muscle tissue. Real-time PCR was adopted to detect the mRNA expression of PINK1, Parkin, p62 and LC3B in rat gastrocnemius muscle tissue. RESULTS: Compared with the blank group, the mitochondria of gastrocnemius muscles showed obvious swelling in the 0 h, 12 h, 24 h, and 48 h model subgroups , autophagosomes were formed in the 12 h and 24 h model subgroups, and the mitochondrial morphology returned to normal gradually in the 72 h model subgroup. The serum MDA contents of rats in 5 model subgroups increased (P<0.01, P<0.05). The contents of SOD and CAT in the subgroups of 0 h, 12 h, 24 h and 48 h decreased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1, Parkin and LC3B in gastrocnemius muscle tissue of rats in 0 h, 12 h and 24 h subgroups were elevated (P<0.01); and the protein and mRNA expression levels of p62 in the 0 h, 12 h, 24 h and 48 h subgroups were reduced (P<0.01, P<0.05). Compared with the model subgroup at the same time point, the myofibril damage and the degree of mitochondrial swelling were mild in each acupuncture pretreatment subgroup, and the numbers of autophagosomes were fewer. The contents of MDA in the acupuncture pretreatment subgroups decreased at 0 h, 12 h, 24 h, and 48 h (P<0.05, P<0.01). The contents of SOD and CAT in the 12 h acupuncture pretreatment subgroup increased (P<0.05, P<0.01). The protein and mRNA expression levels of PINK1 and Parkin in the 0 h, 12 h, and 24 h acupuncture pretreatment subgroups decreased (P<0.01, P<0.05). The protein and mRNA expression levels of LC3B in the 12 h acupuncture pretreatment subgroup decreased (P<0.01), and that of p62 in the 0 h and 24 h acupuncture pretreatment subgroups increased (P<0.01, P<0.05). CONCLUSION The intermittent downhill running centrifugal exercise induces the excessive mitochondrial autophagy. Acupuncture pretreatment may attenuate EIMD, and the underlying mechanism is related to the regulation of PINK1/Parkin signaling pathway expression, reducing oxidative stress damage in skeletal muscle cells, and inhibiting mitochondrial autophagy overactivation.
Animals ; Ubiquitin-Protein Ligases/genetics* ; Male ; Rats ; Acupuncture Therapy ; Protein Kinases/genetics* ; Rats, Sprague-Dawley ; Mitophagy ; Humans ; Muscle, Skeletal/metabolism* ; Physical Conditioning, Animal ; Muscular Diseases/physiopathology* ; Signal Transduction

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Objective To investigate the relationships of the expression levels of BUB1 mitotic checkpoint serine/threonine kinase B(BUB1B)and kinesin family member 11(KIF11)in peripher-al blood with postoperative recurrence in non-muscle-invasive bladder cancer(NMIBC)patients trea-ted with transurethral resection of bladder tumor(TURBT).Methods A retrospective case-control study design was employed.A total of 188 NMIBC patients who received standard TURBT treatment in the 215th Hospital of Shaanxi Nuclear Industry during initial visit from January 2019 to December 2021 were selected as research objects.Patients were followed up for 36 months and divided into re-currence group(n=68)and non-recurrence group(n=120)based on pathological examination re-sults.Additionally,50 healthy individuals who underwent physical examinations during the same period were selected as control group.The levels of BUB1B mRNA and KIF11 mRNA in peripheral blood were compared among the recurrence group,non-recurrence group,and control group.Clinical data were compared between the recurrence and non-recurrence groups.Cox proportional hazards regression models were used to analyze the postoperative follow-up data of NMIBC patients with TURBT.Kaplan-Meier plots were drawn to assess the proportional hazards assumption(PH assumption)of the Cox model.The predictive efficacy of various indicators for postoperative recurrence in NMIBC patients was eval-uated using receiver operating characteristic(ROC)curve.Results The levels of BUB1B mRNA and KIF11 mRNA in peripheral blood in the control group,non-recurrence group,and recurrence group sucessively increased(P＜0.001).The recurrence group had a significantly higher number of patients with pathological T1 staging and multiple tumors compared to the non-recurrence group(P＜0.05).The Kaplan-Meier curves for the number of tumors,pathological staging,BUB1B mRNA,and KIF11 mRNA levels were generally parallel to recurrence rates between the two groups,meeting PH assumption.Multiple tumors,pathological T1 staging,BUB1B mRNA,and KIF11 mRNA levels were independent influencing factors for recurrence in NMIBC patients after TURBT treatment(P＜0.05).ROC curve analysis showed that the areas under the curves(AUCs)for predicting postoper-ative recurrence in NMIBC patients by multiple tumors,pathological T1 staging,BUB1B mRNA,and KIF11 mRNA levels were 0.674,0.746,0.610 and 0.642,respectively.The combined pre-diction using these indicators yielded an AUC of 0.826(95％CI,0.767 to 0.884),with a sensitiv-ity of 86.80％and a specificity of 75.30％,indicating good predictive efficacy.Conclusion Ele-vated levels of BUB1B mRNA and KIF11 mRNA in peripheral blood are significantly associated with postoperative recurrence in NMIBC patients after TURBT and serve as independent risk factors for recurrence.As non-invasive biomarkers,BUB1B mRNA and KIF11 mRNA in peripheral blood com-bined with clinical parameters can significantly improve the predictive efficacy of postoperative recur-rence,providing a new strategy for individualized monitoring.

Objective To evaluate the prognostic value of endosomal sorting complex required for transport(ESCRT)-related genes in osteosarcoma(OS)based on bioinformatics.Methods Preprocessing was performed on 88 OS sequencing samples(with 29 death outcomes)downloaded from the TARGET database and 257 patient clinical information.The Cox proportional hazards model was constructed using the survival package to screen ESCRT genes related to the survival.The STRING database was used to construct a protein-protein interaction(PPI)network,and core genes were selected based on PPI.KEGG enrichment analysis was performed on the selected core genes with more than 5 nodes.Lasso regression analysis was applied to identify ESCRT-related genes more closely related to the prognosis of OS patients.Results A total of 1 486 ESCRT-related genes were identified,of which 164 were associated with the survival.CLTC,MYC,INSR,PTPN1,and TNFRSF1A were identified as core genes related to the prognosis of OS patients.OS patients were randomly divided into a training set(n=44)and a validation set(n=44).In the training set,OS patients in the high-risk group had the significantly shorter overall survival than those in the low-risk group(P<0.05),and the similar results were obtained in the validation set(P<0.01).The ROC(receiver operating characteristic)curve showed an AUC of 0.846 in the training set and 0.877 in the validation set.Prognostic survival analysis and differential analysis of core genes revealed no difference in MYC between high-and low-risk groups in the validation set,and no difference in INSR in the training set.In the overall dataset,all prognostic core genes showed significant differences(P<0.05).Survival analysis of core genes using the R package Survival showed significant differences in survival rates for four genes(CLTC,INSR,PTPN1,TNFRSF1A)except MYC(P>0.05).Univariate independent prognostic analysis identified three genes(TNFRSF1A,PTPN1,MYC)associated with OS survival.Multivariate independent prognostic analysis ultimately identified two key genes(TNFRSF1A,PTPN1)as independent factors influencing OS survival prognosis and closely related to OS patient survival.Conclusion A risk scoring model for OS survival prognosis based on the expression of two key genes,TNFRSF1A and PTPN1,was been successfully constructed using bioinformatics and it can provide more options for clinical treatment and survival prognosis assessment of OS.

Objective:To investigate the clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 105 patients who underwent symmetrical three-port LSG at The First Hospital of Shanxi Medical University from October 2021 to October 2024 were collected. There were 57 males and 48 females, aged 27(range, 19-59)years. Of the 105 patients, 52 cases with continuous Bougie tube use during the surgery were divided into continuous group, while 53 cases with intermittent Bougie tube use were divided into intermittent group. Observation indicators: (1) surgical situations; (2) complications. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 105 patients underwent symmetrical three-port LSG. The operation time was (57±4)minutes versus (76±4)minutes for the continuous group and the intermittent group, volume of intraoperative blood loss was (26±6)mL versus (59±9)mL, time to first out-of-bed activities was (218±8)minutes versus (299±9)minutes, time to first anal exhaust was (19.6±2.9)hours versus (25.8±2.8)hours, visual analogue scale score for pain at 6 hours postoperatively was 2.3±1.0 versus 4.7±1.0, and duration of postoperative hospital stay was (1.5±0.6)days versus (3.1±0.9)days for the two groups, respectively. There were significant differences in the above indicators between the two groups( t=26.92, 22.31, 48.91, 11.15, 13.25, 10.21, P<0.05). (2) Complications. No severe postopera-tive complication occurred in any of the 105 patients. There were 26 cases and 38 cases with nausea and vomiting at 2 hours postoperatively, showing a significant difference between them ( χ2=5.19, P<0.05). Conclusion:Compared to intermittent Bougie tube use, continuous Bougie tube use during symmetrical three-port LSG can significantly shorten operation time and duration of postoperative hospital stay, reduce intraoperative bleeding and postoperative pain, accelerate recovery of patients, and lower the incidence of complications.

In proton therapy,prompt gamma-ray imaging is considered as one of the most promising methods for assessing proton beam range.Prompt gamma-ray imaging detector evaluates the proton beam range based on the prompt gamma-ray distribution obtained by the prompt gamma-ray imaging system,which enables high-precision measurement of the proton beam range.Herein a proton beam range verification algorithm is designed for the newly developed prototype of the range verification detector(pixelated prompt gamma-ray imaging detector),which verifies the range estimation accuracy of the prototype for different phantoms and different energies of homogeneous media through Monte Carlo simulation.The results show that the accuracy of the proton beam range verification algorithm is within 0.5 mm of the safety margin error of the Bragg peak,and the measurement accuracy is significantly improved with the increase of the number of protons,indicating that the prototype algorithm is feasible for proton beam range verification.

Objective:To investigate the clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 105 patients who underwent symmetrical three-port LSG at The First Hospital of Shanxi Medical University from October 2021 to October 2024 were collected. There were 57 males and 48 females, aged 27(range, 19-59)years. Of the 105 patients, 52 cases with continuous Bougie tube use during the surgery were divided into continuous group, while 53 cases with intermittent Bougie tube use were divided into intermittent group. Observation indicators: (1) surgical situations; (2) complications. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 105 patients underwent symmetrical three-port LSG. The operation time was (57±4)minutes versus (76±4)minutes for the continuous group and the intermittent group, volume of intraoperative blood loss was (26±6)mL versus (59±9)mL, time to first out-of-bed activities was (218±8)minutes versus (299±9)minutes, time to first anal exhaust was (19.6±2.9)hours versus (25.8±2.8)hours, visual analogue scale score for pain at 6 hours postoperatively was 2.3±1.0 versus 4.7±1.0, and duration of postoperative hospital stay was (1.5±0.6)days versus (3.1±0.9)days for the two groups, respectively. There were significant differences in the above indicators between the two groups( t=26.92, 22.31, 48.91, 11.15, 13.25, 10.21, P<0.05). (2) Complications. No severe postopera-tive complication occurred in any of the 105 patients. There were 26 cases and 38 cases with nausea and vomiting at 2 hours postoperatively, showing a significant difference between them ( χ2=5.19, P<0.05). Conclusion:Compared to intermittent Bougie tube use, continuous Bougie tube use during symmetrical three-port LSG can significantly shorten operation time and duration of postoperative hospital stay, reduce intraoperative bleeding and postoperative pain, accelerate recovery of patients, and lower the incidence of complications.

Objective:To investigate the relationship between CBCT imaging changes of condyle and clinical features,and related risk factors in patients with temporomandibular disorders(TMD).Methods:453 patients with TMD were enrolled and underwent CBCT scan for bilateral temporomandibular joints(TMJ),3D reconstruction of the TMJs was analyzed.Logistic regression analysis was performed to investigate the relationship between condylar bone changes and TMD clinical features.Results:Patients＜18 years old were more likely to have condylar bone changes than the adults.The symptoms of pain and restricted mouth opening were more likely to be detected in the condylar bone change group(n=133)than in the normal condylar bone group(n=320).The incidence of brux-ism in the normal condylar bone group was higher than that in the condylar bone change group.Univariate logistic regression analysis showed that only bruxism(OR=0.550),pain(OR=1.844)and mouth restriction(OR=2.024)were included in the regression equa-tion.Multivariate logistic regression analysis showed that,due to the protective effect of bruxism,the OR value of pain decreased from 1.844 to 1.791,and the OR value of mouth restriction decreased from 2.024 to 1.847.Conclusion:The condylar bone change in TMD patients more likely occur in puberty or patients with pain and restricted mouth opening.Bruxism may be a protective factor in the occurrence of condylar bone changes in TMD patients.

Objectives:To identify the risk factors associated with delirium in intensive care unit (ICU) hospitalization of sepsis patients and construct a clinical prediction model to to provide a reference for the prevention and control of delirium in sepsis patients.Methods:Data were collected of sepsis patients admitted in the Intensive Care Unit in the Second Affiliated Hospital of Soochow University from September 2020 to August 2022.The patients were divided into delirium group and non-delirium group according to whether delirium occurred or not. Comparing of the differences in general and clinical data between the two groups, the independent risk factors for delirium were screened by backward stepwise regression method, and the delirium risk prediction model was constructed and evaluated. An independent risk factor analysis for delirium was conducted using a backward stepwise regression approach to identify significant predictors. A delirium risk prediction model was constructed based on the identified risk factors, followed by a comprehensive evaluation of the model's performance.Results:A total of 381 sepsis patients were included in the study, 114 patients (29.9%) developed delirium during the ICU hospitalization. Univariate analysis revealed statistically significant differences ( P< 0.05) between the delirium and non-delirium groups for several factors including age ≥ 65 years, blood transfusion, use of midazolam, use of adrenaline, APACHEⅡ score>15, SOFA score>4, metabolic acidosis, urea>7.1 mmol/L, coagulation disorders, lactate levels, and platelet count. Multivariate analysis identified age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders as independent risk factors for delirium in sepsis patients during ICU hospitalization.The predictive model was evaluated with an area under the ROC curve of 0.813, a non-significant Hosmer-Lemeshow goodness-of-fit test ( P=0.957>0.05), and a Brier score of 0.149 (<0.25), indicating good predictive performance and calibration. Clinical decision and impact curves demonstrated the model's favorable clinical applicability. Conclusions:The occurrence of delirium in ICU sepsis patients closely associate with six factors: age ≥ 65 years, use of midazolam, APACHEⅡ score>15, metabolic acidosis, urea>7.1 mmol/L, and coagulation disorders. This sepsis delirium prediction model has good clinical predictive ability and clinical applicability.

Cancer remains a major global health challenge, with conventional treatments like chemotherapy and radiotherapy often hindered by significant side effects, lack of specificity, and limited efficacy in advanced cases. Among emerging therapeutic strategies, mRNA vaccines have shown remarkable potential due to their adaptability, rapid production, and capability for personalized cancer treatment. This review provides an in-depth analysis of messenger RNA (mRNA) vaccines as a therapeutic approach for cancer immunotherapy, focusing on their molecular biology, classification, mechanisms, and clinical studies. Derived from reported literature and data on clinicaltrials.gov, it examines studies on mRNA vaccines encoding tumor-specific antigens (TSAs), tumor-associated antigens (TAAs), immunomodulators, and chimeric antigen receptors (CARs) across various cancer types. The review highlights the ability of mRNA vaccines to encode TSAs and TAAs, enabling personalized cancer treatments, and classifies these vaccines into non-replicating and self-amplifying types. It further explores their mechanisms of action, including antigen presentation and immune activation, while emphasizing findings from clinical studies that demonstrate the potential of mRNA vaccines in cancer therapy. Despite their promise, challenges remain in enhancing delivery systems, improving immunogenicity, and addressing tumor heterogeneity. Overcoming these obstacles will require further investigation to fully harness the potential of mRNA vaccines in personalized cancer treatment.
Humans ; Cancer Vaccines/immunology* ; Neoplasms/immunology* ; mRNA Vaccines/therapeutic use* ; Immunotherapy/methods* ; Antigens, Neoplasm/genetics* ; RNA, Messenger/therapeutic use*