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*

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 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 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.

Objective:To investigate the application value of pre-suture craniotomy combined with intracranial pressure monitoring in surgery for posttraumatic acute diffuse brain swelling (PADBS).Methods:One hundred and fifty-seven patients with PADBS admitted to our hospital from February 2015 to December 2019 were chosen in our study; 68 patients (control group), admitted to our hospital from February 2015 to June 2017, underwent controlled decompression under intracranial pressure monitoring; and 89 patients (treatment group), admitted to our hospital from June 2017 to December 2019, were performed pre-suture craniotomy combined with controlled decompression under intracranial pressure monitoring. The craniotomy time, brain tissue exposure time, cranial closure time, incidence of acute encephalocele, and Glasgow outcome scale (GOS) scores at 6 months after injury were retrospectively analyzed and compared between the two groups.Results:As compared with those in the control group, the patients in the treatment group had significantly longer intraoperative craniotomy time ([19.2±1.6] min vs. [15.4±1.4] min), significantly shorter exposure time of brain tissues ([18.5±2.4] min vs. [26.3±2.2] min), significantly shorter time of cranial closure ([11.2±1.5] min vs. [18.3±2.1] min), and statistically lower incidence of acute encephalocele (22.5% vs. 38.2%), P<0.05). The good prognosis rate of the treatment group (70.8%) was significantly higher than that of the control group (50.0%), and the mortality rate (6.7%) was statistically lower than that of the control group (17.6%, P<0.05). Conclusion:Pre-suture craniotomy combined with controlled decompression under intracranial pressure monitoring can shorten the time of cranial closure and brain tissue exposure, reduce the incidence of acute encephalocele, and ultimately improve the prognosis of patients with posttraumatic acute diffuse brain swelling.

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.

Objective:To explore the effects of dietary glycemic load (GL) during first trimester on the risk of gestational diabetes mellitus (GDM).Methods:A prospective study was conducted among healthy women with singleton pregnancy at 8-14 weeks of gestation in a maternity out-patient clinic of maternal-and-child health care institution in Chengdu, Sichuan province. Information on dietary intake during the first trimester was collected through a 3-day 24-hour dietary recall. Glycemic index (GI) values were obtained from China Food Composition Tables (Standard Edition) and International Tables of Glycemic Index and Glycemic Load Values (2008). Dietary GL and GLs of staple foods were calculated based on GI values and the amount of carbohydrate consumed per day. Diagnostic criteria of GDM was followed the Guidelines for Diagnosis and Treatment of Pregnancy Diabetes in China (2014), and used on participants who underwent an oral glucose tolerant test during 24-28 weeks of gestation. Log-binomial regression models were used to explore the associations between both quartiles of dietary GL, GLs of staple foods and the risks of GDM,respectively.Results:The medians of dietary GL and GL of staple foods were 145.70 (113.23-180.85) and 121.05 (89.08-155.70), respectively. The median GL of both rice and tubers were 73.14 (43.89-107.50) and 3.43 (0.00-9.84), respectively. After adjusting for the age at pregnancy, pre-pregnancy body mass index and other confounding factors, results of log-binomial regressions analysis showed that when compared with the lowest quartile of dietary GL group, the third and highest quartiles of dietary GL groups increased the risk of GDM ( RR=1.47, 95% CI: 1.20-1.80; RR=1.31, 95% CI: 1.04-1.64), respectively. Compared with the lowest quartile of GL of staple foods, the third and highest quartiles of GL of staple foods groups also increased the risk of GDM ( RR=1.28, 95% CI: 1.04-1.58; RR=1.27, 95% CI: 1.02-1.60), respectively. The third and highest quartiles of GL of rice groups increased the risk of GDM ( RR=1.30, 95% CI: 1.06-1.59; RR=1.28, 95% CI: 1.03-1.59), respectively, than the lowest quartile of GL of rice group. When compared with the lowest quartile of GL of tubers group, the highest quartile of GL of tubers group increased the risk of GDM ( RR=1.30, 95% CI: 1.09-1.54). However, we did not notice the effects of wheat GL and coarse grain GL on the risk of GDM. Conclusions:A positive association was found between dietary glycemic load and the risk of GDM. Higher dietary glycemic load, especially in rice and tubers during first trimester, seemed to have increased the risk of GDM.

Objective:To investigate the effect of decompression of optic nerve canal for traumatic optic neuropathy (TON) via lateral supraorbital approach.Methods:A retrospective case series study was performed to analyze clinical data of 23 TON patients admitted to First People's Hospital of Huzhou from December 2013 to June 2019. There were 16 males and 7 females, aged 17-51 years [(34.3±2.2)years]. Degree of visual impairment included count fingers in 4 patients, hand motion in 4, light perception in 9 and loss of light perception in 6. Visual evoked potential examination (VEP) was performed in 15 patients before surgery. The amplitude of P100 completely disappeared in 5 patients, and the amplitude of P100 was lower than the lower limit of normal value and the latency prolonged in 10 patients. The time from injury to operation was 3 h-14 days [(3.3±0.6)days]. All patients underwent decompression of optic nerve canal via supralateral orbital approach, and dural repair was performed simultaneously in 11 patients with dural rupture. Intraoperative fractures and meningeal tears, duration of operation, blood loss, and hospitalization duration were recorded. Combined with the classical visual acuity improvement assessment method and the World Health Organization (WHO) low vision and blind grading standard, visual acuity was compared before operation, at 10 days and 3 months after operation. Glasgow Coma Scale (GCS) was used to evaluate patients' state of consciousness in the course of the disease. Glasgow Outcome Scale (GOS) was used to evaluate the prognosis. Incidence of complications was observed as well.Results:All patients were followed up for 12-16 weeks [(13.5±2.4)weeks]. Intraoperative microscopic exploration revealed that all patients had optic nerve canal fracture, 3 patients had frontal fracture with dural rupture, and 8 patients had ethmoid bone fragment with anterior skull base dural rupture. The duration of operation was 108.5-224.3 minutes [(151.8±30.2)minutes], including (32.5±8.4)minutes for craniotomy. The intraoperative blood loss was 90.5-165.3 ml [(121.3±15.5)ml]. The hospitalization was 14-26 days [(19.7±3.4)days]. The visual acuity of 13 patients (57%) improved and 5 patients (39%) relieved from blindness 10 days after operation, showing significant difference compared with the preoperation ( P<0.05). The visual acuity of 17 patients (74%) improved and 9 patients (39%) relieved from blindness at 3 months after operation. There was significant difference in visual acuity examined between 10 days and 3 months after operation ( P<0.05). Six patients were invalid, and 4 of them had no light perception before operation and the amplitude of VEP examination completely disappeared. All patients had GCS of 15 when left the hospital and GOS of 5 at 3 months after operation. One patient had cerebrospinal fluid rhinorrhea and healed after 7 days of supine position. No secondary hematoma, epilepsy or intracranial infection occurred during follow-up. Conclusion:Optic canal decompression via the lateral supraorbital approach can improve visual acuity in early stage and increase the rate of out of blindness, with low postoperative complications and satisfactory functional recovery, which is worthy of clinical application.