Immunomodulatory cancer therapy is witnessing the rise of viral immunotherapy. The oncolytic influenza A virus, although promising in preclinical investigations, remains to be implemented in clinical practice. Recent progress in genetic engineering, coupled with experiential insights, offers opportunities to enhance the therapeutic efficacy of the influenza A virus. This review explores the use of the influenza virus, its attenuated forms, and associated vaccines in cancer immunotherapy, highlighting their respective advantages and challenges. We further elucidate methods for engineering influenza viruses and innovative approaches to augment them with cytokines or immune checkpoint inhibitors, aiming to maximize their clinical impact. Our goal is to provide insights essential for refining influenza A virus-based viral tumor immunotherapies.
Humans ; Neoplasms/immunology* ; Immunotherapy/trends* ; Influenza A virus/immunology* ; Oncolytic Virotherapy/trends* ; Animals ; Cancer Vaccines/therapeutic use* ; Oncolytic Viruses ; Genetic Engineering ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To investigate the reliability and validity of different measurement methods under 30° arthroscopy for quantifying the proportion of glenoid bone defect in bony Bankart lesions of the shoulder joint and validate its preliminary application effect.Methods:Eight intact shoulder glenoid specimens were selected, with no existing defects or deformities, from donors of 4 females and 4 males, with their age at death of 43-67 years [(54.4±8.0)years]. Bone defects of 12.5% and 25% were created in the glenoid at 0° and 45° relative to the longitudinal axis, with two specimens per defect category. The defect proportion in each specimen was quantified using direct measurement and CT-based digital reconstruction and these values served as reference standards for subsequent statistical analysis. Using a combined approach of arthroscopic simulation equipment and cadaveric study, five investigators performed simulated examinations through the standard posterior portal (2 cm medial and 1.5 cm inferior to the posterolateral acromial corner) and the modified posteroinferior portal (2 cm medial and 3 cm inferior to the posterolateral acromial corner) separately. Under 30° arthroscopy, the glenoid bone loss percentage was measured using the bare spot method and secant chord method. The reliability was analyzed for these measurements. Furthermore, using direct physical measurements and CT-based three-dimensional reconstruction data from the same specimens as reference standards, the comprehensive validity of four measurement methods was evaluated (standard posterior portal-bare spot method, standard posterior portal-secant chord method, modified posteroinferior portal-bare spot method, and modified posteroinferior portal-secant chord method). The independent validity of each method was assessed according to bone defect morphology classification to determine differences in measurement accuracy across defect types. In an arthroscopic procedure for a patient with Bigliani type IIIB bony Bankart lesion, the standard posterior portal-secant chord method was applied to quantify the proportion of glenoid bone defects.Results:The mean reference values from direct measurement and CT measurement of glenoid bone defect proportion in eight bony Bankart lesion specimens were 12.71%/12.37%, 13.17%/13.10%, 25.71%/24.9%, 26.6%/26.95%, 13.41%/13.10%, 12.90%/12.59%, 26.42%/25.94%, and 26.73%/27.06%, respectively. Measurements obtained by the five investigators showed intraclass correlation coefficients (ICCs) all greater than 0.90, indicating excellent interobserver agreement. In the validity analysis, the standard posterior portal-secant chord method demonstrated the highest overall validity. Using direct measurement and CT-based measurement as reference standards, the overall validity was (0.90±0.38)% and (1.07±0.53)% for the standard posterior portal-bare spot method, (1.33±0.40)% and (1.51±0.54)% for the modified posteroinferior portal-bare spot method, and (0.53±0.17)% and (0.70±0.38)% ( P<0.05) for the modified posteroinferior portal-secant chord method. In contrast, the standard posterior portal-secant chord method showed an overall validity of (0.10±0.10)% and (0.28±0.39)% ( P>0.05). In subsequent independent validity analyses, the standard posterior portal-secant chord method also demonstrated superior validity across all bone defect subtypes over the other three methods. In a patient with a Bigliani type IIIB bony Bankart lesion, we used the standard posterior portal-secant chord method to quantify the glenoid bone loss in 2 minutes, revealing a defect proportion of 26.6%. An arthroscopic autologous iliac bone graft procedure with single-tunnel elastic fixation guided by this measurement achieved favorable outcomes, with stable reduction, secure internal fixation and favorable recovery of shoulder function at 2 months postoperatively. Conclusion:For various types of bony Bankart lesions, the 30° arthroscopic standard posterior portal-secant chord method provides the most accurate quantification of glenoid bone loss and its preliminary clinical application yields satisfactory results.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective:To investigate the reliability and validity of different measurement methods under 30° arthroscopy for quantifying the proportion of glenoid bone defect in bony Bankart lesions of the shoulder joint and validate its preliminary application effect.Methods:Eight intact shoulder glenoid specimens were selected, with no existing defects or deformities, from donors of 4 females and 4 males, with their age at death of 43-67 years [(54.4±8.0)years]. Bone defects of 12.5% and 25% were created in the glenoid at 0° and 45° relative to the longitudinal axis, with two specimens per defect category. The defect proportion in each specimen was quantified using direct measurement and CT-based digital reconstruction and these values served as reference standards for subsequent statistical analysis. Using a combined approach of arthroscopic simulation equipment and cadaveric study, five investigators performed simulated examinations through the standard posterior portal (2 cm medial and 1.5 cm inferior to the posterolateral acromial corner) and the modified posteroinferior portal (2 cm medial and 3 cm inferior to the posterolateral acromial corner) separately. Under 30° arthroscopy, the glenoid bone loss percentage was measured using the bare spot method and secant chord method. The reliability was analyzed for these measurements. Furthermore, using direct physical measurements and CT-based three-dimensional reconstruction data from the same specimens as reference standards, the comprehensive validity of four measurement methods was evaluated (standard posterior portal-bare spot method, standard posterior portal-secant chord method, modified posteroinferior portal-bare spot method, and modified posteroinferior portal-secant chord method). The independent validity of each method was assessed according to bone defect morphology classification to determine differences in measurement accuracy across defect types. In an arthroscopic procedure for a patient with Bigliani type IIIB bony Bankart lesion, the standard posterior portal-secant chord method was applied to quantify the proportion of glenoid bone defects.Results:The mean reference values from direct measurement and CT measurement of glenoid bone defect proportion in eight bony Bankart lesion specimens were 12.71%/12.37%, 13.17%/13.10%, 25.71%/24.9%, 26.6%/26.95%, 13.41%/13.10%, 12.90%/12.59%, 26.42%/25.94%, and 26.73%/27.06%, respectively. Measurements obtained by the five investigators showed intraclass correlation coefficients (ICCs) all greater than 0.90, indicating excellent interobserver agreement. In the validity analysis, the standard posterior portal-secant chord method demonstrated the highest overall validity. Using direct measurement and CT-based measurement as reference standards, the overall validity was (0.90±0.38)% and (1.07±0.53)% for the standard posterior portal-bare spot method, (1.33±0.40)% and (1.51±0.54)% for the modified posteroinferior portal-bare spot method, and (0.53±0.17)% and (0.70±0.38)% ( P<0.05) for the modified posteroinferior portal-secant chord method. In contrast, the standard posterior portal-secant chord method showed an overall validity of (0.10±0.10)% and (0.28±0.39)% ( P>0.05). In subsequent independent validity analyses, the standard posterior portal-secant chord method also demonstrated superior validity across all bone defect subtypes over the other three methods. In a patient with a Bigliani type IIIB bony Bankart lesion, we used the standard posterior portal-secant chord method to quantify the glenoid bone loss in 2 minutes, revealing a defect proportion of 26.6%. An arthroscopic autologous iliac bone graft procedure with single-tunnel elastic fixation guided by this measurement achieved favorable outcomes, with stable reduction, secure internal fixation and favorable recovery of shoulder function at 2 months postoperatively. Conclusion:For various types of bony Bankart lesions, the 30° arthroscopic standard posterior portal-secant chord method provides the most accurate quantification of glenoid bone loss and its preliminary clinical application yields satisfactory results.

Objective:To evaluate the reliability and validity of different quantitative methods based on CT images to evaluate the proportion of shoulder glenoid defect.Methods:Four shoulder joint specimens with no trauma, osteoarthritis or deformity were used, including 2 females and 2 males; the average age of death was 58±10 years old; all the specimens were prepared with a standard method with no bone defect occurring before preparation. A glenoid bone defect model was established with each specimen being cut into four defect gradient defects of approximately 8%, 16%, 24%, and 32% in proportion in sequence. A total of 16 samples were obtained. Physical photography and CT image reconstruction were performed on the 16 samples respectively. A total of 8 quantitative methods were used to quantify bone defects, which were surface area method, superimposed circle method, Barchilon method, Pico method, Shaha method, Griffith method, Sugaya method, and Giles method. Intraclass correlation (ICC) using a consistency model was used to evaluate reliability. Paired t-test was used to evaluate validity, with the physical measurement of the specimens using the surface area method as the reference standard. Result:The consistency ICC of each quantitative method was greater than 0.9, and all had high reliability. Combining the results of all bone defect gradients and imaging images, the surface area method had the best validity, which was 0.83%±0.75%; the Barchilon method came second, which was 0.91%±0.93%; the superimposed circle method and the Pico method had good validity, which were 0.99%±0.87% and 1.27%±1.09%, respectively; the Shaha method, the Griffith method, and the Sugaya method had poor validity, which were 6.11%±1.56%, 5.06%±1.35%, and 6.02%±1.61%, respectively; the Giles method had the worst validity, which was 8.40%±3.08%. Conclusion:In clinical practice, surface area method and superimposed circle method are the most reliable to quantify the proportion of bone defect if they can be performed. Otherwise, linear measurement of Barchilon method is the favored method while PICO method is the favored method for angle measurement.

Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.

Objective:To evaluate the predictive value of hematological inflammatory markers such as preoperative monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and several tumor-related factors in differentiating malignant and benign primary retroperitoneal tumors (PRTs) .Methods:This study retrospectively collected the data of 159 pathologic confirmed PRTs patients who underwent surgery in the First Affiliated Hospital of Wenzhou Medical University and Taizhou Municipal Hospital between Dec. 2009 and Aug. 2020. Univariate analysis of clinic data was performed to identify the differences between the benign and malignant PRTs. Logistic regression analysis was used to determine the independent predictive parameters for malignant PRTs.Results:Among the 159 patients with PRTs, 80 were malignant, 68 were benign, and 11 were borderline. Contrast with benign and borderline tumor, univariate analysis demonstrated that tumor size, preoperative neutrophil count, platelet count, albumin level, MLR, NLR and PLR exhibited significant differences in malignant tumor (all P<0.05). PLR (HR=1.025, P=0.020) and tumor size (HR=1.085, P=0.006) were independent risk factors for predicting malignant PRTs in the multivariate logistic analyses. According to the ROC curve, the optimal cutoff value of tumor size and PLR for predicting malignant PRTs were 194.85 (sensitivity 38.7%, specificity 93.5%), 8.75 cm (sensitivity 69.3%, specificity 72.7%), respectively. Conclusions:Preoperative PLR is useful in differentiating malignant and benign PRTs and it is an independent risk parameter for malignant PRTs. Preoperative PLR could be considered as a new significant predictor for malignant PRTs.

OBJECTIVE: To investigate the clinical value of analgesia and sedation under bispectral index (BIS) monitoring combined with hydraulic coupled intracranial pressure (ICP) monitoring in severe craniocerebral injury (sTBI). METHODS: (1) A prospective self-controlled parallel control study was conducted. A total of 32 patients with sTBI after craniotomy admitted to the intensive care unit (ICU) of the First People's Hospital of Huzhou from December 2020 to July 2021 were selected as the research objects. ICP was monitored by Codman monitoring system and hydraulically coupled monitoring system, and the difference and correlation between them were compared. (2) A prospective randomized controlled study was conducted. A total of 108 sTBI patients admitted to the ICU of the First People's Hospital of Huzhou from August 2021 to August 2022 were selected patients were divided into 3 groups according to the random number table method. All patients were given routine treatment after brain surgery. On this basis, the ICP values of the patients in group A (35 cases) were monitored by Codman monitoring system, the ICP values of the patients in group B (40 cases) were monitored by hydraulic coupling monitoring system, and the ICP values of the patients in group C (33 cases) were monitored combined with hydraulic coupling monitoring system, and the analgesia and sedation were guided by BIS. The ICP after treatment, cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, complications and Glasgow outcome score (GOS) at 6 months after surgery were compared among the 3 groups. In addition, patients in group B and group C were further grouped according to the waveforms. If P₁ = P₂ wave or P₂ and P₃ wave were low, they were classified as compensatory group. If the round wave or P₂ > P₁ wave was defined as decompensated group, the GOS scores of the two groups at 6 months after operation were compared. RESULTS: (1) There was no significant difference in ICP values measured by Codman monitoring system and hydraulic coupling monitoring system in the same patient (mmHg: 11.94±1.76 vs. 11.88±1.90, t = 0.150, P = 0.882; 1 mmHg≈0.133 kPa). Blan-altman analysis showed that the 95% consistency limit (95%LoA) of ICP values measured by the two methods was -4.55 to 4.68 mmHg, and all points fell within 95%LoA, indicating that the two methods had a good correlation. (2) There were no significant differences in cerebrospinal fluid drainage time, ICP monitoring time, ICU stay time, and incidence of complications such as intracranial infection, intracranial rebleeding, traumatic hydrocephalus, cerebrospinal fluid leakage, and accidental extubation among the 3 groups of sTBI patients (P > 0.05 or P > 0.017). The ICP value of group C after treatment was significantly lower than that of group A and group B (mmHg: 20.94±2.37 vs. 25.86±3.15, 26.40±3.09, all P < 0.05), the incidence of pulmonary infection (9.1% vs. 45.7%, 42.5%), seizure (3.0% vs. 31.4%, 30.0%), reoperation (3.0% vs. 31.4%, 40.0%), and poor prognosis 6 months after operation (33.3% vs. 65.7%, 65.0%) were significantly lower than those in group A and group B (all P < 0.017). According to the hydraulic coupling waveform, GOS scores of 35 patients in the compensated group were significantly higher than those of 38 patients in the decompensated group 6 months after operation (4.03±1.18 vs. 2.39±1.50, t = 5.153, P < 0.001). CONCLUSIONS The hydraulic coupled intracranial pressure monitoring system has good accuracy and consistency in measuring ICP value, and it can better display ICP waveform changes than the traditional ICP monitoring method, and has better prediction value for prognosis evaluation, which can replace Codman monitoring to accurately guide clinical work. In addition, analgesia and sedation under BIS monitoring combined with hydraulic coupled ICP monitoring can effectively reduce ICP, reduce the incidence of complications, and improve the prognosis, which has high clinical application value.
Humans ; Intracranial Pressure ; Prospective Studies ; Monitoring, Physiologic/methods* ; Craniocerebral Trauma ; Analgesia ; Cerebrospinal Fluid Leak

Objective:To compare the efficacy and safety between WangShiBaoChiWan and mosapride in the treatment of functional dyspepsia (FD).Methods:From September 2019 to September 2020, patients with postprandial fullness and early satiation who met the Rome Ⅳ criteria for FD diagnosis were enrolled from 15 hospitals, including the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital), Beijing Traditional Chinese Medicine Hospital Affiliated to Capital Medical College. The subjects were randomly divided into WangShiBaoChiWan (experimental) group and mosapride (control) group in the ratio of 1∶1. The treatment regimens were WangShiBaoChiWan+ mosapride simulator, WangShiBaoChiWan simulator+ mosapride, respectively with a treatment period of 2 weeks. The primary efficacy outcome was the improvement rates of main symptoms before and after treatment, the secondary efficacy primary efficacy outcome was the total clinical effective rate and the change of the single symptom score. And the safety indicator included adverse events. Independent sample t-test, paired t-test and chi-square test were used for statistical analysis. Results:A total of 251 FD patients were enrolled in the full analysis set, including 124 in the experimental group and 127 in the control group; 241 FD patients were in the per-protocol analysis set, including 117 in the experimental group and 124 in the control group. The analysis of per-protocol analysis set showed that the improvement rates of the main symptoms of the experimental group and the control group were (66±29)% and (60±30)%, respectively, and the difference was not statistically significant ( P>0.05). The improvement rate of the main symptoms of the experimental group reached 117% of that of the control group, which exceeded the expected non-inferiority standard of 80%. The total clinical effective rates of the experimental group and the control group were 76.07% (89/117) and 75.81% (94/124), respectively, and the difference was not statistically significant ( P>0.05). The results of full analysis set showed that the incidence of adverse events of the experimental group and the control group was 1.62% (2/124) and 1.57% (2/127), respectively, and the difference was not statistically significant ( P>0.05). There were no serious adverse events in the two groups. Conclusion:The improvement rate of the main symptoms of WangShiBaoChiWan is not inferior to that of mosapride in the treatment of FD, and it has good safety.

Objective:To evaluate the effect of transfusion-free techniques on the prognosis of liver transplant patients.Methods:The recipients of adult liver transplantation at Tianjin First Central Hospital from August to December 2019 were included in the clinical observation. Liver transplantation without allogeneic blood transfusion was performed through anesthesia management techniques such as acute hemodilution or phlebotomy without volume replacement,maintaining decreased baseline central venous pressure and cell saver. According to the actual results,the patients were divided into two groups: transfusion-free group( n=21) and allogeneic transfusion group( n=28). There were 13 males and 8 females aged of (56.3±11.6) years in the transfusion-free group;and there were 16 males and 12 females aged (54.3±14.2)years in the allogeneic transfusion group. The transplant recipients who had not adopted transfusion management strategy from January to July 2019 were included as control group(27 males and 13 females,aged of (58.9±14.1)years). The clinical data of patients in perioperative period were collected to compare whether there were differences in the recovery of liver function and early complications among the three groups, one-way ANOVA test, rank-sum test, and χ 2 test were used for data analysis. Results:The amount of intraoperative blood loss in both the transfusion-free group and the transfusion group was less than that in the control group((454.2±271.3)ml vs.(673.6±333.4)ml vs.(890.3±346.7)ml; q=-6.342,-5.286,both P<0.05).The duration of stay in ICU of the transfusion-free group was less than that of the transfusion group and control group((36.4±9.1)hours vs.(44.3±14.9)hours vs.(58.2±21.1)hours; q=-4.432,-3.824,both P<0.05).The mean ALT level at 7 days after operation was significantly lower in the transfusion-free group than in the control group((56.8±32.1)U/L vs.(89.6±45.6)U/L; q=-3.358, P<0.05). Conclusions:The improvement of multi-disciplinary transfusion management technology aimed at transfusion-free liver transplantation can effectively reduce intraoperative hemorrhage and help to avoid surgical transfusion. Transfusion-free liver transplantation is beneficial to the early postoperative recovery,and its long-term clinical significance is worthy of further clinical research.