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BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.
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Objective:To investigate the effects of extracorporeal carbon dioxide removal (ECCO 2R) combined with continuous renal replacement therapy (CRRT) on respiratory efficiency and diaphragm function in patients with acute respiratory distress syndrome (ARDS) received mechanical ventilation. Methods:A prospective randomized controlled study was conducted. Sixty patients with mild to moderate ARDS admitted to the department of respiratory and critical care medicine of Henan Provincial People's Hospital from January 2019 to January 2021 were enrolled, and they were divided into observation group and control group according to the random number table method, with 30 cases in each group. All patients received antibiotics, anti-inflammatory, and mechanical ventilation therapy. On this basis, the observation group received ECCO 2R and CRRT, while the control group received bedside CRRT. Baseline data including gender, age, etiology, acute physiology and chronic health evaluationⅡ(APACHEⅡ), etc., were recorded. Arterial blood gas analysis [including arterial partial pressure of oxygen (PaO 2), arterial partial pressure of carbon dioxide (PaCO 2), and oxygenation index (PaO 2/FiO 2)] was performed at 12 hours and 24 hours during the treatment, and respiratory mechanics parameters [including tidal volume, respiratory rate, maximum expiratory pressure (MEP), and maximum inspiratory pressure (MIP)] were recorded, and rapid shallow breathing index (RSBI) was calculated. The levels of glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum were detected by enzyme-linked immunosorbent assay (ELISA). Diaphragm thickness and diaphragm activity were measured by ultrasonography at 24 hours during the treatment. Results:There were no significantly differences in age, gender, etiology, and APACHEⅡ score between the two groups, indicating that the baseline data of the two groups were balanced and comparable. Compared with the 12 hours after treatment, the PaO 2 and PaO 2/FiO 2 in the observation group significantly increased, PaCO 2 significantly decreased, RSBI significantly decreased, MEP and MIP significantly increased, and serum GSH-Px and MDA significantly decreased, while SOD significantly increased at 24 hours during the treatment. In the control group, only PaCO 2 significantly decreased. Compared with the control group, the PaCO 2 significantly decreased in the observation group at 12 hours and 24 hours [mmHg (1 mmHg≈0.133 kPa): 55.05±7.57 vs. 59.49±6.95, 52.77±7.88 vs. 58.25±6.92, both P < 0.05], but no significantly differences in PaO 2 and PaO 2/FiO 2. Compared with the control group, the observation group showed significant decreases in RSBI at 12 hours and 24 hours (times·min -1·L -1: 85.92±8.83 vs. 90.38±3.78, 75.73±3.86 vs. 90.05±3.66, both P < 0.05), significant increases in MEP and MIP [MEP (mmH 2O, 1 mmH 2O≈0.01 kPa): 86.64±5.99 vs. 83.88±4.18, 93.70±5.59 vs. 85.04±3.73; MIP (mmH 2O): 44.19±6.66 vs. 41.17±3.13, 57.52±5.28 vs. 42.34±5.39, all P < 0.05], and significant decreases in serum GSH-Px and MDA [GSH-Px (mg/L): 78.52±8.72 vs. 82.10±3.37, 57.11±4.67 vs. 81.17±5.13; MDA (μmol/L): 7.84±1.97 vs. 8.71±0.83, 3.67±0.78 vs. 8.41±1.09, all P < 0.05], as well as a significant increase in SOD (U/L: 681.85±49.24 vs. 659.40±26.47, 782.32±40.56 vs. 676.65±51.97, both P < 0.05). Compared with the control group, the observation group showed significant increases in diaphragm thickness and diaphragm activity at 24 hours of treatment [diaphragm thickness (cm): 1.93±0.28 vs. 1.40±0.24, diaphragmatic thickening fraction: (0.22±0.04)% vs. (0.19±0.02)%, quiet breathing diaphragm displacement (cm): 1.42±0.13 vs. 1.36±0.06, deep breathing diaphragm displacement (cm): 5.11±0.75 vs. 2.64±0.59, all P < 0.05]. Conclusion:ECCO 2R combined with CRRT can reduce work of breathing and oxidative stress levels in ARDS patients receiving non-invasive ventilation, and protect diaphragm function.
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Objective:To evaluate the effect of ultrasound-guided adductor canal combined with knee joint posterior capsule space block on the recovery period delirium in elderly patients undergoing total knee arthroplasty (TKA).Methods:A total of 68 elderly patients who underwent unilateral TKA at the Nanjing First Hospital from December 2021 to December 2022 were selected. They were randomly divided into a control group ( n=34) and an observation group ( n=34) using a random number table method. Both groups received general anesthesia, and the observation group received ultrasound-guided myofascial tube combined with knee joint posterior capsule space block before the surgery began. The incidence of delirium within 24 hours after surgery was mainly observed in two groups of patients. The surgical time, recovery time, intraoperative blood loss, infusion volume, total use of propofol and remifentanil were recorded; The resting and motor Visual Analogue Scale (VAS) scores of the patient were recorded at 4, 8, and 24 hours postoperatively. The patient′s serum tumor necrosis factor-α (TNF-α) and melatonin levels were measured on the day before surgery, the evening after surgery, and the first day after surgery. The subjective sleep quality score was recorded on the first day after surgery; The total dosage of sufentanil for patient-controlled intravenous analgesia (PCIA) within 24 hours after surgery, the effective number of compressions (P1) and actual number of compressions (P2) of PCIA, and the number of cases of additional oxycodone analgesia were recorded; The occurrence of respiratory depression, excessive sedation, nausea, and vomiting within 24 hours after surgery was recorded; The occurrence of complications of nerve block in the observation group was recorded. Results:The incidence of delirium during the recovery period in the observation group was lower than that in the control group ( P<0.05). The dosage of propofol and remifentanil in the observation group was lower than that in the control group (all P<0.05), and the awakening time was shorter than that in the control group ( P<0.05). The VAS scores at rest and exercise at 4, 8, and 24 hours after surgery in the observation group were lower than those in the control group (all P<0.05). Compared with the day before surgery, the observation group showed an increase in melatonin levels on the night after surgery ( P<0.05) and an increase in TNF-α levels on the first day after surgery ( P<0.05); The control group had a decrease in melatonin levels on the first day after surgery ( P<0.05), and an increase in TNF-α levels on the night and day after surgery (all P<0.05). The serum melatonin levels in the observation group were higher than those in the control group on the evening and first day after surgery (all P<0.05), and TNF-α levels were lower than those in the control group (all P<0.05). The subjective sleep quality score of the observation group showed that the total dosage of PCIA sufentanil, P1, P2, and the number of cases of additional oxycodone analgesia within 24 hours after surgery were lower than those of the control group (all P<0.05). The incidence of nausea in the control group (13 cases, 38.2%) was higher than that in the observation group (3 cases, 8.8%) ( P<0.05). Conclusions:In elderly patients undergoing unilateral TKA under general anesthesia, preoperative use of ultrasound-guided adductor tube combined with knee joint posterior capsule space block can effectively reduce the occurrence of postoperative delirium.
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Objective:To comprehensively evaluate the performance of the iterative cone beam CT (iCBCT) imaging mode of Varian linear accelerators and to explore its specific advantages in clinical application.Methods:The kV cone beam CT (CBCT) imaging systems of Halcyon 2.0, Edge, and VitalBeam linear accelerators from Tianjin Medical University Cancer Institute & Hospital were selected, among which Halcyon 2.0 and Edge were equipped with the iCBCT imaging mode. The Penta-Guide phantom was used to evaluate the registration accuracy of iCBCT imaging modes. The accuracy of treatment couch position was measured by a ruler. The image quality of the iCBCT and conventional CBCT modes of various imaging devices were analyzed using the CatPhan604 phantom. The imaging beam-on time and reconstruction time were measured to assess image acquisition efficiency. The uniformity, spatial resolution, contrast, contrast-to-noise ratio (CNR), image acquisition time and reconstruction time between two imaging modes were statistically analyzed by t-test. Results:The maximum deviations of image registration measurement results of the iCBCT mode for Halcyon 2.0 and Edge accelerators compared to the standard values were 0.7 mm and 0.6 mm, respectively. The treatment couch position error of all devices was less than 1 mm. The iCBCT images under head scanning protocol primarily improved the uniformity and CNR. Compared to conventional CBCT images, Halcyon iCBCT increased the uniformity and CNR by 2.50% ( P<0.001) and 78.85% ( P<0.001), respectively, while Edge increased them by 2.18% ( P<0.001) and 86.42% ( P<0.001), both superior to VitalBeam CBCT images. Under pelvis scanning protocols, iCBCT images primarily improved the CNR compared to conventional CBCT images. Halcyon and Edge iCBCT increased the CNR by 113.57% ( P<0.001) and 133.87% ( P<0.001), respectively, both superior to VitalBeam CBCT images. In terms of image acquisition efficiency, the average reconstruction times for Halcyon and Edge iCBCT images increased by 7.28 s and 15.53 s, respectively, and the total image acquisition time of Halcyon accelerator was the shortest. Conclusions:While ensuring the registration accuracy, iCBCT imaging mode can significantly improve the CNR of images and improve the uniformity of images under head scanning protocol. The Halcyon imaging system can enhance image acquisition efficiency.
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Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.
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Objective:To explore the clinical efficacy of 125I seeds implantation combined with transcatheter arterial chemoembolization (TACE) in the treatment of primary liver cancer. Methods:A retrospective analysis of data from 40 patients with primary liver cancer at the Northern Theater General Hospital from January 2018 to December 2020 (26 males, 14 females, age 41 to 82 years) was performed. Among them, 21 patients were in treatment group and underwent 125I seeds implantation combined with TACE treatment, while 19 patients were in control group and received TACE treatment. Alpha-fetoprotein (AFP) levels between the two groups were compared, effective rate and disease control rate (DCR) of the two groups were analyzed, and overall survival (OS) and progression-free survival (PFS) were observed. Data were analyzed by using Mann-Whitney U test, χ2 test, Kaplan-Meier method and log-rank test. Results:Two months after 125I seeds implantation, the effective rates of treatment group and control group were 76.19%(16/21) and 8/19, respectively ( χ2=4.83, P=0.028); the DCRs were 90.48%(19/21) and 11/19, respectively ( χ2=4.21, P=0.040). AFP levels in both groups decreased significantly, with treatment group showing a greater decrease rate (0.87(0.84, 0.90) and 0.66(0.65, 0.67); z=5.42, P<0.001). No serious adverse reaction was observed in either group. The median OS of treatment group and control group were 18.2 and 10.6 months, respectively ( χ2=10.98, P=0.037); the median PFS of the two groups were 8.4 and 6.1 months, respectively ( χ2=7.54, P=0.041). Conclusion:125I seeds implantation combined with TACE treatment can exert a synergistic and enhancing effect in the treatment of primary liver cancer.
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Objective:To investigate the predictive value of serum uric acid/albumin ratio (sUAR) for acute kidney injury (AKI) after cardiac valve surgery.Methods:The clinical data of adult patients undergoing cardiac valve surgery under cardiopulmonary bypass from January 2021 to December 2021 from the Heart Center of Henan Provincial People's Hospital were collected retrospectively, and the sUAR was calculated. All patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac valve surgery, and the differences of clinical data between the two groups were compared. Multivariate logistic regression model was used to analyze the independent correlation factors of AKI after cardiac valve surgery. The receiver operating characteristic (ROC) curve was used to evaluate the performance of relevant indicators.Results:A total of 422 patients were enrolled, including 194 females (46.0%), 141 hypertension patients (33.4%) and 172 atrial fibrillation patients (40.8%). They were 57 (50, 65) years old. Their sUAR was 8.13 (6.57, 9.54) μmol/g, and hemoglobin was 135 (125, 145) g/L. There were 142 cases in AKI group and 280 cases in non-AKI group, and the incidence of AKI after cardiac valve surgery was 33.6%. Age, atrial fibrillation rate, baseline serum creatinine, N terminal pro B type natriuretic peptide, serum urea,serum uric acid, blood glucose and sUAR were higher in the AKI group than those in the non-AKI group (all P<0.05), and estimated glomerular filtration rate, lymphocyte count,hemoglobin and serum albumin were lower in the AKI group than those in the non-AKI group (all P<0.05). The median cardiopulmonary bypass time of patients in the AKI group was slightly longer than that in the non-AKI group, but the difference was not statistically significant [159 (125, 192) min vs. 151 (122, 193) min, Z=-0.797, P=0.426], and there were no statistically significant differences in other indicators between the two groups. The results of multivariate logistic regression analysis showed that sUAR ( OR=1.467, 95% CI 1.308-1.645, P<0.001), age ( OR=1.045, 95% CI 1.020-1.072, P<0.001), atrial fibrillation ( OR=2.520, 95% CI 1.580-4.020, P<0.001), hemoglobin ( OR=0.984, 95% CI 0.971-0.997, P=0.015) were the independent correlation factors. ROC curve analysis showed that the area under the curve ( AUC) of sUAR predicting AKI after cardiac valve surgery was 0.710 (95% CI 0.659-0.760, P<0.001) with a sensitivity of 85.2% and specificity of 45.0% for the sUAR cut-off point of 7.28 μmol/g. The AUC for the diagnosis of AKI after cardiac valve surgery was 0.780 (95% CI 0.734-0.825, P<0.001) with a sensitivity of 72.5% and specificity of 71.8% for the combination of sUAR with age, hemoglobin and atrial fibrillation. Conclusions:For patients undergoing cardiac valve surgery under cardiopulmonary bypass, preoperative high sUAR is an independent risk factor for postoperative AKI, and sUAR has a certain predictive value for postoperative AKI.
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Objective:To investigate the effect of distilled water on the viability of human lens epithelial cells (LECs) cultured in vitro. Methods:A total of 156 anterior capsule specimens were collected from 156 patients (156 eyes) who were diagnosed with age-related cataract during phacoemulsification combined with intraocular lens implantation from May to December 2020 in Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School.The 156 specimens were divided into 312 small pieces.Of the 312 pieces, 157 pieces were divided into normal control group (23 pieces), positive control group (10 pieces), balanced salt solution (BSS) immersion group (61 pieces) and distilled water immersion group (63 pieces) using computer-generated random numbers.Normal control group received no treatment.Positive control group was directly fixed with a mass fraction of 4% histiocytes fixative solution.For the 61 pieces in BSS immersion group, 20 pieces were soaked for 1 minute, 21 pieces for 2 minutes, and 20 pieces for 3 minutes.For the 63 pieces in distilled water immersion group, 20 pieces were soaked for 1 minute, 23 pieces for 2 minutes, and 20 pieces for 3 minutes.Another 125 pieces were selected to simulate the cataract aspiration-irrigation according to the treatment in BSS immersion group and distilled water immersion group respectively, plus rinse in a bottle containing BSS at a height of 70 cm for 1 minute.Cell viability was detected by trypan blue-eosin staining.LECs density, dead cell count, cell death rate and percentage of shedding (%) were calculated.Of the remaining 30 pieces, every 15 pieces were divided into normal control group, BSS immersion group, and distilled water immersion for 1, 2 and 3 minutes groups, with 3 pieces in each group.BSS immersion group was immersed for 3 minutes, and the other four groups were treated as mentioned above, and the LECs structure of the four groups was observed by light microscopy and transmission electron microscopy.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School (No.2019-248-01). Written informed consent was obtained from each subject.Results:The boundaries of LECs in BSS treatment groups were clear, and there was no significant difference in morphology compared with normal control group.With time increasing, LECs in distilled water treatment groups gradually swelled, and the boundaries of dead cells were not clear.There were significant differences in LECs density, dead LECs count and LECs mortality ( F=13.459, 98.918, 130.600; all at P<0.001). The LECs density was lower in 2-minute and 3-minute distilled water treatment groups than in normal control group, showing statistically significant differences (both at P<0.05). The dead LECs count and LECs mortality were higher in 1-minute, 2-minute and 3-minute distilled water treatment groups than in normal control group and BSS treatment groups for the same time, and the differences were statistically significant (all at P<0.05). Only a few shed LECs were seen in normal control group, 1-minute, 2-minute and 3-minute BSS treatment groups, and BSS immersion combined rinse group.After different time of soaking, there were more shed LECs in distilled water immersion combined rinse group, and the range of LECs shedding increased with the extension of distilled water immersion.There was a significant difference in the shedding percentage of LECs among different groups ( F=123.670, P<0.001). The shedding percentages of LECs at different time points were higher in distilled water immersion groups and distilled water immersion combined rinse groups than in normal control group, and the difference was statistically significant (all at P<0.05). The shedding percentage of LECs increased significantly in distilled water immersion groups with the extension of immersion.Light microscopy showed that the cells were destroyed in 1-minute, 2-minute and 3-minute distilled water treatment groups, and some LECs shed in the 2-minute and 3-minute treatment groups.Transmission electron microscopy showed cell lysis and destruction, suborganelles swelling, disruption of intercellular junctions in 1-minute, 2-minute and 3-minute distilled water treatment groups, loose attachment between cells and capsule in the 2-minute and 3-minute treatment groups, and cell detachment from capsule in the 3-minute treatment group. Conclusions:Distilled water immersion leads to LECs death in a time-dependent manner, and distilled water immersion combined with rinse can remove LECs on the lens capsule.
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Objective:To investigate the inhibitory effect of indocyanine green (ICG) on biological behavior and transdifferentiation of human lens epithelial cells (HLECs) and its mechanism.Methods:HLECs were divided into blank control group, 5% glucose solution (GS) group and 0.5% ICG group, 1.5% ICG group and 2.5% ICG group, which were treated with balanced salt solution, 5% GS and 0.5%, 1.5% and 2.5% ICG solutions for 3 minutes, respectively, and then were incubated in fresh medium for 24 hours.The apoptosis level of HLECs was detected by flow cytometry.The expression levels of apoptosis-related proteins, Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), caspase-3 and caspase-9 were detected by Western blot.Cell proliferation was detected via the cell counting kit-8 (CCK-8) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay.The migration ability of HLECs was detected by cell scratch assay.Cell migration and invasion were determined by Transwell assays.The expression levels transdifferentiation-related proteins, α-smooth muscle actin (α-SMA), nerve calcium adhesion protein (N-cadherin), fibronectin (FN) and vimentin were assessed by Western blot.Results:The apoptosis rates of blank control group, 5% GS group, 0.5% ICG group, 1.5% ICG group and 2.5% ICG group were (4.35±0.60)%, (4.63±0.19)%, (8.17±0.69)%, (13.90±0.33)% and (23.08±1.12)%, with a statistically significant difference in the overall comparison ( F=412.74, P<0.05). The apoptosis rate was significantly higher in 0.5% ICG group, 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group (all at P<0.05). The relative expressions of caspase-3, caspase-9 and Bax proteins were significantly higher in 0.5% ICG group, 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group, and the relative expression of Bcl-2 protein was lower in 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group, and the differences were statistically significant (all at P<0.05). The rate of EdU-positive cells was significantly lower in 0.5% ICG group, 1.5% ICG group and 2.5% ICG groups than in blank control group and 5% GS group (all at P<0.05). The survival rate of cells was significantly lower in 0.5% ICG group, 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group (all at P<0.05). The migration rates of scratch cells were significantly lower in 0.5% ICG group, 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group, and the differences were statistically significant (all P<0.05). The number of migrating cells and the number of invading cells were significantly lower in 0.5% ICG group, 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group (all at P<0.05). The relative expressions of α-SMA, N-cadherin and FN were significantly lower in 0.5% ICG group, 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group, and the relative expression of vimentin was lower in 1.5% ICG group and 2.5% ICG group than in blank control group and 5% GS group, and the differences were statistically significant (all at P<0.05). Conclusions:ICG can promote HLECs apoptosis and inhibit HLECs proliferation, migration, invasion and transdifferentiation in a concentration-dependent manner.
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Objective:To investigate the clinical effects of different approaches of ultrasound-guided adductor canal block (ACB) in postoperative analgesia after total knee arthroplasty (TKA) and its impact on joint function recovery.Methods:Fifty-eight patients undergoing unilateral TKA at Nanjing First Hospital from March 2021 to March 2022 were randomly divided into two groups: group A (ultrasound-guided proximal ACB, n=29) and group B (ultrasound-guided distal ACB, n=29). Both groups received intravenous patient-controlled analgesia (PCIA) combined with ultrasound-guided ACB. The resting and exercise Visual Analog Scale (VAS) scores at various time points after surgery, the total amount of sufentanil used for PCIA, the effective compression times (P1) and actual compression times (P2) of PCIA, the analgesia satisfaction score, the number of additional tramadol analgesia cases, the quadriceps muscle strength and knee joint activity at various time points after surgery, and the complications were recorded for analysis. Results:The resting and exercise VAS scores at 4, 8, 12, 24, and 48 hours after surgery in the group B were lower than those in the group A (all P<0.05). The total amount of Sufentanil used for PCIA, P1 and P2, and the number of additional tramadol analgesia cases in the group B were less than those in the group A (all P<0.05). The analgesia satisfaction score in the group B was higher than that in the group A ( P<0.05). The quadriceps muscle strength at 24 hours after surgery and the knee joint activity at 24 and 48 hours after surgery in the group B were higher than those in the group A (all P<0.05). The incidence of nausea in the group B was lower than that in the group A ( P<0.05). Conclusions:Ultrasound-guided distal ACB is more effective in relieving postoperative pain after TKA, reducing the dosage of opioid drugs, improving quadriceps muscle strength and joint mobility, reducing the incidence of adverse reactions, and is conducive to the recovery of knee joint function.
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Objective:To evaluate the safety and feasibility of applying injectable cross-linked sodium hyaluronate isolation gel in radical hypofractionated radiation therapy for prostate cancer.Methods:In this prospective study, patients at Beijing Hospital who were pathologically diagnosed with clinical stage T 1-2N 0M 0 prostatic acinar adenocarcinoma by puncture and underwent radical radiation therapy were included. All patients received ultrasound-guided cross-linked sodium hyaluronate isolation gel injection and image-guided intensity-modulated radiation therapy (IG-IMRT). The prescription dose was moderately hypofractionated, with a prescription dose of 60 Gy in 20 fractions for 5 times a week, once daily, which was delivered to 95% of the planning target volume (PTV) of prostate and seminal vesicle. Analyze the prostate rectal spacing (PRS) at the baseline, on the day of injection, during the radiotherapy, 1 month and 3 months after radiotherapy, changes in rectal volume before and after injection, and incidence of rectum-related side effects. The changes in all indexes before and after injection were analyzed by using t-test. Results:A total of 13 patients were enrolled from March 2022 to February 2023. The isolation gel maintained morphologic stability without significant spatial changes during radiotherapy, and the mid-prostate had the best effect, with PRS up to 1 cm. At 3 months after radiotherapy, the isolation gel was seen to decreased in volume with a certain absorptive capacity. The irradiated volume of rectum was decreased significantly in all patients after gel injection, and the mean volumes of rectal V 60 Gy , V 50 Gy , V 30 Gy , and V 20 Gy before and after injection were 1.923% vs. 0.280%, 10.255% vs. 3.172%, 29.602% vs. 18.800%, and 49.452% vs. 40.259% (all P<0.005). The average values (range) of rectal V 60 Gy , V 50 Gy , V 30 Gy , V 20 Gy decreases were 84.9%( 29% - 100%), 69.6%(27%-100%), 36.3%(0%-75%), and 17.8%(0%-50%), respectively. No grade 3-4 side effects occurred in all patients, and there were no common grade 1-2 rectal side effects such as diarrhea, rectal bleeding, proctitis and anal pain, etc. Only one patient developed grade 1 constipation during radiotherapy. Conclusion:Injection of Chinese made cross-linked sodium hyaluronate isolation gel can significantly reduce the irradiated volume of rectum and the incidence of rectal toxicities in prostate cancer patients undergoing radical radiotherapy.
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Objective:To evaluate the clinical value of CT-guided 125I seeds implantation combining with 89SrCl 2 to relieve pain after failure of external irradiation in patients with bone metastases from prostate cancer. Methods:Clinical data of 48 patients (age 56-85 years) with bone metastases from prostate cancer admitted to General Hospital of the Northern Theater Command from January 2019 to June 2021 were retrospectively analyzed. Patients were treated with 125I seeds implantation combining with 89SrCl 2 (group A) and 89SrCl 2 alone (group B), respectively. Independent-sample t test and repeated measures analysis of variance were used to evaluate the differences of pain level (most severe pain, least pain, mean pain and current pain) scores and bone pain interference scores between 2 groups before and after treatment (before treatment, 3 d, 4 weeks, 8 weeks and 12 weeks after treatment). Prostate specific antigen (PSA), free PSA (fPSA) and alkaline phosphatase (ALP) 12 weeks after treatment of 2 groups were also compared by using independent-sample t test. Results:In group A, a total of 722 seeds were implanted in 39 bone metastases in 23 patients, and the implantation successful rate was 97.44%(38/39). There were 25 patients in group B. In group A, the most severe pain, mean pain and current pain scores decreased with time ( F values: 3.71-22.47, all P<0.05). Except for the scores at 3 d posttreatment, most severe pain, mean pain, and current pain scores at different times showed significant differences with those before treatment (all P<0.05). There were also differences in the most severe pain, mean pain, and current pain scores in group B before and after treatment ( F values: 2.45-2.52, P values: 0.044-0.049), with scores decreasing first (till 8 weeks after treatment) and increasing later. The most severe pain, mean pain, and current pain scores 8 week after treatment were lower than those before treatment (all P<0.05), but all the four scores at 12 weeks were not significantly different from those before treatment ( P values: 0.057-0.693). At 12 weeks after treatment, the differences in the most severe pain, mean pain and current pain scores between 2 groups were statistically significant ( t values: 2.04-3.41, P values: 0.001-0.047). Bone pain interference scores 12 weeks after treatment in group A were higher than those in group B ( t values: 2.04-3.16, P values: 0.022-0.047), and PSA, fPSA and ALP 12 weeks after treatment in group A were significantly lower than those in group B ( t values: 4.38-6.82, P values: 0.012-0.042). Conclusion:CT-guided 125I seeds implantation combined with 89SrCl 2 is feasible and effective for the treatment of bone pain after failed external irradiation in patients with prostate cancer bone metastases, especially for the combination of fulminant pain.
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Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.
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Objective To investigate the expression and clinical significance of TM9SF3 in lung adenocarcinoma (LUAD). Methods TCGA and GEPIA databases were used to screen the differentially-expressed TM9SF family molecules and analyze their effects on patient prognosis with LUAD. The expression and localization of TM9SF3 in LUAD patients were verified by a human proteomic mapping database, Western blot assay, and polymerase chain reaction assay. Herein, the GSEA was used for the signal pathway enrichment analysis of TM9SF3-related genes. Meanwhile, the TIMER database and CIBERSORT algorithm were used to analyze the correlation between differentially-expressed TM9SF3 and the degree of immune cell infiltration. Results The expression of TM9SF3 in LUAD was significantly increased and had a significant adverse effect on the prognosis of LUAD patients. In addition, immunoblotting and polymerase chain reaction confirmed that TM9SF3 was highly expressed in LUAD. Meanwhile, the genes related to TM9SF3 expression were mainly enriched in cell signaling pathways regulating immune cell activity. The expression of TM9SF3 was significantly correlated with the expression changes of six immune cells. Conclusion TM9SF3 is differentially expressed in LUAD and may be used as a potential prognostic marker for LUAD patients. TM9SF3 can also change the level of immune cell infiltration in LUAD patients and is expected to be a new potential target for LUAD immunotherapy.
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Objective:To analyze the effect of dexmedetomidine combined with thoracic paravertebral block (TPVB) on sleep quality, serum interleukin-6 (IL-6) and high mobility group protein (HMGB-1) levels in patients undergoing thoracoscopic pulmonary surgery.Methods:The clinical data of 90 patients who received thoracoscopic pulmonary surgery from January 2020 to January 2021 in Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. Among them, 45 patients were given dexmedetomidine combined with TPVB before operation (experiment group), and 45 patients were given TPVB before operation (control group). The indexes of sleep quality were recorded, including Pittsburgh sleep quality index (PSQI) and total sleep time 24 and 48 h after operation. The visual analogue score (VAS) during quiet and cough 1, 6, 12, 24 and 48 h after operation were recorded. The serum substance P (SP), 5-hydroxytryptamine (5-HT), C-reactive protein (CRP), IL-6 and HMGB-1 before operation and 1 d after operation were detected. The adverse reactions were compared between 2 groups.Results:The PSQI 24 and 48 h after operation in experiment group was significantly lower than that in control group: (11.38±4.61) scores vs. (13.65±2.72) scores and (8.78±3.79) scores vs. (10.95±2.81) scores, the total sleep time was significantly longer than that in control group: (7.71±2.64) h vs. (5.49±2.10) h and (9.75±3.14) h vs. (7.82±2.67) h, and there were statistical differences ( P<0.01). The VAS during quiet and cough 1, 6 and 12 h after operation in experiment group was significantly lower than that in control group, and there was statistical difference ( P<0.01); there was no statistical difference in the VAS during quiet and cough 24 and 48 h after operation between 2 groups ( P>0.05). There were no statistical differences in serum SP, 5-HT, CRP, IL-6 and HMGB-1 before operation between 2 groups ( P>0.05); the SP, 5-HT, CRP, IL-6 and HMGB-1 1 d after operation in experiment group were significantly lower than those in control group: (132.59±10.34) ng/L vs. (141.57±12.26) ng/L, (0.73±0.11) μmol/L vs. (0.95±0.09) μmol/L, (32.46±3.54) mg/L vs. (38.53±4.12) mg/L, (145.67±24.68) ng/L vs. (162.79±23.51) ng/L and (70.35±6.81) ng/L vs. (92.36±7.08) ng/L, and there were statistical differences ( P<0.01). The incidence of adverse reactions in experiment group was significantly lower than that in control group: 20.00% (9/45) vs. 48.89% (22/45), and there was statistical difference ( χ2 = 8.32, P = 0.004). Conclusions:Dexmedetomidine combined with TPVB can effectively improve postoperative sleep quality of patients undergoing thoracoscopic pulmonary surgery, relieve pain, and reduce postoperative serum pain mediators and inflammatory factors, with fewer adverse reactions.
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Objective:To study the safety and efficacy of a treatment protocol using immune checkpoint inhibitors (ICIs) and antiangiogenic targeted drugs (AATDs) in converting 41 patients with initially unresectable to resectable hepatocellular carcinoma (HCC).Methods:The data of 41 patients with initially unresectable HCC treated with immunotherapy combined with targeted therapy from December 2018 to April 2021 in Chinese PLA General Hospital were analysed. There were 34 males and 7 females, aged (51.8±10.7) years. The clinical characteristics, conversion to resectable HCC, adverse drug reactions, surgical data and postoperative complications were analysed. Patients were followed-up by outpatients clinics or telephone calls.Results:There were 5 patients with Chinese Liver Cancer Staging (CNLC)-Ⅰb, 4 with CNLC-Ⅱ, 28 with CNLC-Ⅲa and 4 with CNLC-Ⅲb before the treatment protocol. Among them, 28 patients had portal vein tumor thrombosis (PVTT) and 4 had retroperitoneal lymph node metastases. All patients had a mean tumor diameter of (9.16±4.43) cm before and (6.49±4.69) cm after the treatment protocol. The latter was based on the last assessment before hepatectomy. The efficacy of the treatment protocol in converting unresectable to resectable HCC was assessed by the modified Response Evaluation Criteria in Solid Tumors after 3-15 cycles (median dose cycles, 5) of protocal therapy: 15 patients achieved a complete response; 15 patients achieved a partial response; 6 patients had a stable disease, and 5 patients had a progressive disease. 21 patients (51.2%) experienced adverse reactions associated with drug treatment, which resolved with symptomatic treatment or brief discontinuation of the therapy. All patients underwent successful hepatectomy. Postoperative complications of grade Ⅱ or higher occurred in 9 patients (22.0%). The cumulative overall survival rates at 6 months, 1 year and 2 years from diagnosis were 100.0%, 92.6% and 64.7% respectively. The cumulative overall survival rates at 6 months, 1 year and 2 years after surgery were 95.1%, 74.7% and 60.8%, and the recurrence-free survival rates at 6 months, 1 year and 2 years after surgery were 87.8%, 56.7% and 48.6%, respectively.Conclusions:This study provided preliminary evidences that surgical resection after immunotherapy combined with targeted therapy in patients with initially unresectable HCC was safe and efficacious.
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Objective:To investigate the safety and efficacy of combining programmed death-1 (PD-1) with tyrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC) before liver transplantation(LT).Methods:The data of six males with a mean ± s. d. age of (57.5±4.3) years who were treated with PD-1 inhibitors combined with TKIs for advanced HCC before LT at Beijing You'an Hospital, Capital Medical University and the First Medical Center of Chinese PLA General Hospital were retrospectively analysed. The tumor stagings, the use of PD-1 inhibitors and TKIs with their discontinuation in pre-LT/post-LT liver function recovery durations, incidences of complication. The tumor recurrence and disease-free survival rates were determined on follow-up of these patients at outpatients clinics.Results:For the 6 patients included in this study, four patients were classified by the Barcelona Clinic Liver Cancer Staging (BCLC) as C and the China Liver Cancer Staging (CNLC) as Ⅲa, and two patients were classified by the BCLC staging as B and the CNLC asⅡb. The mean cycle of PD-1 inhibitor used was 5.5 (1-20), and the mean duration of PD-1 inhibitor discontinuation was 19.5 (12-45) days pre-LT. All patients who were treated with PD-1 inhibitors combined with TKIs reached the liver transplantation standard, and all successfully underwent orthotopic liver transplantation. The liver function recovered well without any serious complications post-LT. All the patients survived without developing any acute rejection or other complications. The follow-up time ranged from 8.2 to 27.3 months, with a median of 11.9 months. No patients had died, and 2 patients developed tumor recurrence. The median (range) tumor-free survival time was 10.9 (2.9-27.3) months.Conclusion:Patients with advanced HCC could benefit from combined PD-1 inhibitors with TKIs therapy pre-LT. There were no increased incidences of acute rejection and other complications post-LT.
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Objective:To evaluate the efficacy of subomohyoid anterior suprascapular nerve block (SSNB) in the patients undergoing arthroscopic shoulder surgery with general anesthesia.Methods:Sixty patients of either sex, aged 18-64 yr, with body mass index of 18-30 kg/m 2, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, scheduled for elective arthroscopic shoulder surgery, were divided into 2 groups ( n=30 each) using a random number table method: SSNB group (S group) and interscalene brachial plexus block group (I group). Before induction, 0.375% ropivacaine hydrochloride 15 ml was injected between C 5-C 6 nerve roots in group I and around the anterior suprascapular nerve in group S under ultrasound guidance.Diaphragmatic excursion, occurrence and degree of diaphragmatic paralysis, decrease in SpO 2, dyspnea, Horner syndrome and sensory block in the C 5-T 1 dermatomes were assessed at 30 min after injection.The intraoperative consumption of remifentanil, extubation time, and length of post-anesthesia care unit stay were recorded.Quality of Recovery-15 score for patient′s satisfaction with analgesia, effective pressing frequency of analgesic pump, requirement for rescue analgesia, nausea and vomiting and nerve block-related complications within 24 h after surgery were recorded. Results:Compared with group I, the incidence of diaphragmatic paralysis was significantly decreased, the degree of diaphragmatic paralysis was reduced, diaphragmatic excursion was increased, the amplitude of decrease in SpO 2 was reduced, the incidence of dyspnea and Horner syndrome was decreased, extubation time was shortened ( P<0.05), and no significant change was found in the incidence of sensory block in the C 5-T 1 dermatomes, intraoperative consumption of remifentanil, effective pressing frequency of analgesic pump, requirement for rescue analgesia, score for patient′s satisfaction with analgesia, incidence of nausea and vomiting, length of post-anesthesia care unit stay, or Quality of Recovery-15 score in group S ( P>0.05). Conclusions:The subomohyoid anterior SSNB not only provides reliable perioperative analgesia, but also reduces the risk of diaphragmatic paralysis when used in the patients undergoing arthroscopic shoulder surgery with general anesthesia.
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Objective:To investigate the incidence of acute kidney injury (AKI) following pancreaticoduodenectomy and related risk factors in elderly patients.Methods:The clinical data of elderly patients who underwent pancreaticoduodenectomy in Henan Provincial People′s Hospital from January 2017 to June 2020 were collected retrospectively. According to the changes of serum creatinine within 48 h or 7 days after operation, the patients were divided into AKI group and non-AKI group. The basic clinical characteristics of the two groups were compared, and the incidence of AKI was calculated. Multivariate logistic regression model was used to analyze the risk factors of postoperative AKI.Results:A total of 322 elderly patients were enrolled, with age of (67.1±5.2) years old (60-85 years old) and 186 males (57.76%). Among 322 elderly patients, there were 41 patients (12.73%) suffering from AKI following pancreaticoduodenectomy. Compared with the non-AKI group, the level of bilirubin in AKI group was higher ( Z=-2.012, P=0.044), and the level of hemoglobin in AKI group was lower ( Z=-2.111, P=0.035). Multivariate logistic regression analysis showed that increased preoperative total bilirubin ( OR=1.003, 95% CI 1.000-1.006, P=0.027) and postoperative exploratory laparotomy ( OR=3.936, 95% CI 1.071-14.460, P=0.039) were the independent influencing factors for AKI after pancreaticoduodenectomy in elderly patients. Conclusions:The incidence of AKI after pancreaticoduodenectomy in elderly patients is 12.73%. Preoperative high bilirubin and postoperative exploratory laparotomy may be the independent risk factors for AKI after pancreaticoduodenectomy in elderly patients.
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Objective:To investigate the effect of electroporation-mediated local gene therapy on the expression of Wnt3a and β-catenin in callus of distraction gap during mandibular distraction osteogenesis of rabbits.Methods:The experiments were conducted in the laboratory of the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from September 2019 to December 2019. Forty eight New-Zealand rabbits were randomly divided into control group (group A), gene therapy group (group B) and normal saline group (group C), with 16 rabbits in each group. After bilateral mandible osteotomy and distractors were implanted, the distractors were activated at a speed of 0.8 mm/d on 4th day, postoperatively, and lasted for 7 days, followed by consolidation period. Group A distracted only, group B was subject to local injection of recombinant plasmid pIRES-hBMP2-hVEGF165 in the distraction gap and electroporation stimulation at the beginning of activation distractors; and group C local injection of the same dose of normal saline in the distraction gap and electroporation stimulation at the beginning of activation distractors. Four animals in each group were sacrificed on the day at the end of distraction, 7th, 14th, 28th days of consolidation period, respectively. The callus in the distraction gap was taken for immunohistochemical staining and RT-PCR to detect the expression of Wnt3a and β-catenin, and image analysis was performed. SPSS 22.0 statistical software was used for data analysis.Results:Immunohistochemical staining showed that Wnt3a and β-catenin were mainly located in the cytoplasm and nuclei of fibroblasts, chondrocytes and osteoblasts in callus tissue. Immunohistochemistry and RT-PCR showed that the expression of Wnt3a and β-catenin reached a peak at the end of distraction. With the disappearance of distraction tension, the expression of Wnt3a and β-catenin gradually decreased. After gene therapy intervention, the expression of Wnt3a and β-catenin was significantly increased, and the expression of Wnt3a and β-catenin in group B was the highest at each time point, with statistically significant difference compared with groups A and C ( F=96.3, P<0.01). Conclusions:Gene therapy promotes the expression of Wnt3a and β-catenin in the callus of distraction gap, regulating the balance of the bone reconstruction system and thus promoting the formation of new bone in the distraction gap.