[Traditional Chinese medicine for treatment of echinococcosis: a review].

Echinococcosis is a zoonotic parasitic disease caused by infection with Echinococcus species. As the drug of first choice for treatment of echinococcosis, albendazole suffers from problems of large doses and remarkable adverse reactions in clinical therapy. Development of novel drugs against echinococcosis is of urgent need. Recently, great advances have been achieved in the research on traditional Chinese medicine for treatment of echinococcosis. This review summarizes the progress of researches on traditional Chinese medicine for treatment of echinococcosis, aiming to provide insights into development of anti-echinococcosis drugs.

A comparison of size exclusion chromatography-based tandem strategies for plasma exosome enrichment and proteomic analysis.

Proteomic analysis of exosomes from human plasma faces a tremendous challenge mainly due to the low abundance of the exosome itself and the complexity of the plasma matrix. Therefore, enrichment of exosomes from human plasma is an essential and indispensable step for large scale and in depth proteomic analysis. Size exclusion chromatography (SEC) is one of the most extensively used methods for exosome isolation from human plasma and many SEC-based tandem methods were established in order to increase the purity of the enriched exosomes and thus the accuracy of the proteomic analysis. To compare the advantages and disadvantages of the different isolation methods and subsequently to promote the establishment of a standardized method for plasma proteomic research, the capacities of the direct SEC method, the combination of SEC with ultracentrifugation (SEC-UC), ultrafiltration (SEC-UF), and titanium dioxide microspheres (SEC-TiO2) were systematically evaluated for exosome isolation from human plasma and thus proteomic analysis. The results demonstrated that the SEC-based tandem methods were superior to the direct SEC method in the purity of exosomes isolated from human plasma. Additionally, the SEC-UC method possessed the highest number of the total identified proteins and the overlapped proteins with the top 100 exosome markers in comparison with the other methods. The SEC-TiO2 method displayed the biggest capacity for plasma protein deleting. We expect that the research will have more beneficial values in the field of exosome research.

[The mediating role of resilience between social capital at work and anxiety of medical staff].

Objective: To explore the influence of social capital at work on anxiety of medical staff, and the mediating role of resilience. Methods: From March to May 2022, a total of 201 medical staff in the Affiliated Hospital of Jining Medical University were investigated with the General Information Questionnaire, Workplace Social Capital Scale, Connor-Davidson Resilience Scale (CD-RISC-10) and Generalized Anxiety Disorder-7 (GAD-7) . K-S method was used for normdity test of econometic voriobles, and normal distribution data were represented by Mean±SD, Pearson correlation analysis and linear regression analysis were used to test correlation between variables and mediating effect, and Bootstrap method was carried out by SPSS macro program PROCESS v3.5 to verify the mediating effect. Results: The detection rate of anxiety was 59.20% (119/201) in medical staff. The scores of social capital at work (28.90±5.83) and resilience (31.55±4.98) were negatively correlated with the score of anxiety (7.20±2.06) (r=-0.338, -0.510, P<0.001) , while the score of social capital at work was positively correlated with resilience (r=0.392, P<0.001) . Workplace social capital positively predicted resilience (ß=0.392, P<0.001) , and both workplace social capital (ß=-0.222, P=0.001) and resilience at work (ß=-0.423, P<0.001) negatively predicted anxiety score. The direct effect of social capital in the workplace of medical staff on anxiety was -0.222 (95%CI: -0.349~-0.095, P=0.001) , and the indirect effect of resilience on anxiety was -0.166 (95%CI: -0.265~-0.080) . The resilience of medical staff had a partial mediating effect between workplace social capital and anxiety, which accounted for 42.78% of the total effect. Conclusion: The resilience of medical staff has a partial mediating effect between workplace social capital and anxiety. Workplace social capital can not only directly affect the anxiety of medical staff, but also indirectly affect it through resilience.

Stereotactic Body Radiotherapy (SBRT) for Sacral Metastases: Deviation from Recommended Target Volume Delineation Predicts Higher Risk of Local Failure.

PURPOSE/OBJECTIVE(S): A international consensus recommendation was published to guide target volume delineation specific to sacral stereotactic body radiotherapy (SBRT). We report outcomes after sacrum SBRT, focusing on the impact of contouring deviation on local failure (LF) risk, with an aim to validate this guideline. MATERIALS/METHODS: All patients who underwent SBRT to any level between S1 and S5 from 2010 to 2021 were identified from a prospectively maintained institutional database. The primary outcome was magnetic resonance-based LF. Secondary outcomes included vertebral compression fracture (VCF) and overall survival (OS). Cumulative LF and VCF rates were calculated per segment using the competing risk analysis method. Kaplan Meier analysis was used to estimate OS per patient. Cox proportional hazards model was used to assess predictive factors of LF, VCF, and OS. RESULTS: A total of 215 treated sacral segments in 112 patients were retrospectively reviewed. The median follow-up was 13 months (range, 0.4-116.9). The median age was 64 years (range, 18-86), and 56% were male. Most patients (52%) had treatment to a single segment. The median clinical target volume (CTV) was 129.2 cc (range, 5.8-753.5). Most segments were treated with 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Thirty-one percent of segments were of radioresistant histology (gastrointestinal, kidney, melanoma, sarcoma, or thyroid primary), and 51% had extraosseous disease. Sixteen percent of segments were under-contoured per consensus guidelines, with incomplete coverage of the involved sector (71%), omission of the adjacent uninvolved sector (17%), or both (11%) as the causes for deviation. The cumulative incidence of LF was 18.4% (95% CI 13.5-24.0) at 12-months and 23.1% (95% CI 17.6-29.0) at 24-months. On multivariate analysis (MVA), under-contouring (HR 2.4, 95% CI 1.3-4.7, p = 0.008), radioresistant histology (HR 2.4, 95% CI 1,4-4.1, p = 0.001), and extraosseous extension (HR 2.5, 95% CI 1.3-4.7, p = 0.005) were predictors of increased risk of LF. The LF rates at 12/24-months were 15.1%/18.8% for segments contoured per guideline versus 31.4%/40.0% for those under-contoured. The cumulative incidence of VCF was 7.1% (95% CI 4.1-11.1) at 12-months and 12.3% (95% CI 8.2-17.2) at 24-months. On MVA, female gender was the only risk factor for VCF (HR 2.3, 95% CI 1.1-5.2, p = 0.04). The median OS was 29.5 months (95% CI 17.5-59.2). On MVA, primary kidney (HR 4.7, 95% CI 1.7-12.5, p = 0.002) or lung histology (HR 3.4, 95% CI 1.3-8.5, p = 0.010), the presence of liver (HR 2.8, 95% CI 1.2-6.4, p = 0.016) or lung (HR 2.5, 95% CI 1.3-5.1, p = 0.008) metastases, ECOG performance status 2 or 3 (HR 3.3, 95% CI 1.2-8.2, p = 0.013), and the presence of sensory or motor deficit (HR 2.6, 95% CI 1.2-5.4, p = 0.012) were prognostic for worse OS. CONCLUSION: Sacral SBRT is associated with high rates of efficacy and an acceptable VCF risk. Adherence to target volume delineation consensus guidelines reduces the risk of LF.

Staged Stereotactic Radiosurgery as a Novel Adaptive Approach to Salvage Previously Irradiated Brain Metastases.

PURPOSE/OBJECTIVE(S): We report outcomes specific to a novel 3 fraction (frx) staged stereotactic radiosurgery (St-SRS) regimen designed to salvage metastases previously irradiated and considered to be at high risk of radiation necrosis (RN). MATERIALS/METHODS: A total of 24 patients with 55 metastases treated with our 3 frx St-SRS approach were reviewed. Prior to each frx, patients were re-simulated and planned with a new MRI to allow for treatment adaption. The primary endpoint was the cumulative incidence of local failure (LF) and secondary endpoints included tumor dynamics and RN rates. RESULTS: The median follow up was 9.0 months (range: 2.7-40.1 months) and median age was 59-years (range: 32-84). Primary cancers were of breast (44%), lung (33%), melanoma (22%), and gastro-intestinal (1%) origin. Individual metastases treated with St-SRS had initially failed surgery and post-op cavity hypofractionated SRS (HSRS) for 2/55 (4%), SRS alone for 19/55 (34%), whole brain radiation (WBRT) alone for 6/55 (11%), HSRS for 2/55 (4%), and prior SRS and WBRT exposure for 28/55 (51%). 46/55 (84%) were prescribed 8 Gy, 8 Gy, 4 Gy; 8/55 (14%) had 6 Gy, 6 Gy, 4 Gy and 1/55 (2%) had 8 Gy, 8 Gy, 6 Gy. The median number of weeks between frx was 2.6 (range: 1.0-6.8). The median of the mean and maximum target doses were 9.7 Gy (range: 5.4-11.7 Gy) and 12.4 Gy (range, 7.5-16.0 Gy) respectively. The median prescription isodose line was 62% (range: 50-85%). The mean lesion volume and diameter was 3.8cc (range: 0.05-24.8cc) and 1.6cm (range: 0.2-4.4cm), respectively. The mean percent target volume coverage, Paddick Conformality Index and Gradient Index were 100% (range: 97-100%), 0.7 (range: 0.1-0.9), and 3.2 (range: 2.5-6.7), respectively. The mean volume change between staged frxs was -4.2% (range: -69.3 to +63.1%), and based on the first and last St-SRS MRI was -10.8% (range: -86.6% to +68.7%). The crude LF rate was 27%. The median time to LF was 3.4 months (range: 1.2-7.4 months). Amongst those with a LF, 7/15 (46%) were melanoma, 6/15 (40%) HER2 positive breast cancer, 1/15 (7%) gastrointestinal and 1/15 (7%) non-small cell lung carcinoma. 8/15 (53%) had prior WBRT and SRS exposure, 1/16 (7%) surgery and cavity HSRS, 5/15 (33%) SRS alone and 1/15 (7%) WBRT alone. Only asymptomatic RN events were observed in 4/55 (7%). CONCLUSION: St-SRS is a promising approach to salvage previously irradiated brain metastases, including prior SRS, with a favorable rate of RN. Tumor volume dynamics between stages can be significant warranting adaptive replanning.

Stereotactic Body Radiotherapy (SBRT) for Breast Cancer Spinal Metastases is Associated with Low Rates of Long-Term Local Failure (LF) and Vertebral Compression Fracture (VCF) Independent of Molecular Status.

PURPOSE/OBJECTIVE(S): There is limited outcome data specific to breast cancer spinal metastases following spine SBRT. This study aims to report outcomes specific to breast cancer spinal metastases receiving spine SBRT and determine the implication of biomarker status. MATERIALS/METHODS: We have been maintaining a prospective database since the inception of the spine SBRT program. A retrospective review identified 168 breast cancer patients with 409 spinal segments treated with spine SBRT between January 2008 and January 2023. Molecular subtypes were grouped based on luminal A, luminal B, basal, and HER2 enriched. Patients were followed with q3-monthly full-spine MRI and a clinical assessment. The primary endpoint was MRI-based local failure (LF), and secondary endpoints were overall survival (OS) and vertebral compression fracture (VCF). RESULTS: The median follow-up was 33 months (range, 3.3-123 months). Amongst the 168 patients, the majority were ECOG 0 or 1 (95%), neurologically intact (94%), polymetastatic (74%), and either luminal A (71%) or luminal B (8%). A total of 17% of patients were HER2+ve versus 83% HER2-ve. Of 409 treated segments the majority (76%) had no prior radiation or surgery (de novo), were SINS stable (60%), had either no or low-grade epidural disease (86%) and treated with 24-28 Gy in 2 fractions (73%). The LF and OS rates at 1, 3, and 5 years were 5%, 11%, and 14%, respectively, and 91%, 65%, and 45%, respectively, independent of molecular subtype on univariate analyses. The cumulative risk of VCF at 2 and 5 years was 7% and 10%, respectively. CONCLUSION: We observe, in the largest breast cancer spine cohort to date, excellent long-term local control rates independent of molecular sub-group, and acceptable VCF rates.

Patterns of Adaptive Replanning in Proton Therapy for Thoracic Malignancies.

PURPOSE/OBJECTIVE(S): Theability to deliver high doses of localized radiation therapy (RT) while preferentially sparing surrounding normal tissue makes the use of proton beam therapy (PBT) advantageous for thoracic malignancies. However, these traits also make PBT more susceptible to treatment related changes to the tumor or target volume, patient anatomy or surrounding tissue. This may result in increased need for adaptive re-planning during PBT. We present a single institution experience examining patterns of PBT adaptive re-planning in patients treated for thoracic malignancies. MATERIALS/METHODS: Consecutive patients treated with PBT for thoracic malignancies from 2017-2022 at an academic proton center were retrospectively analyzed. Patients were treated with intensity modulated proton therapy (IMPT) either once or twice daily (BID), with or without concurrent systemic therapy. Patients with lung and thymic malignancies were included. Quality assurance CT (QACT) scans were assessed for dosimetric changes. Number and frequency of QACTs was determined by departmental policy and clinical factors such as histology, cancer stage and concurrent systemic therapy. Statistical comparisons of the frequency of replans and pathological and patient characteristics were performed with two-tailed Fisher's exact tests and Chi-Square tests. RESULTS: Of the 340 patients who were retrospectively analyzed, 80 (24%) required replanning during treatment. Median age was 67 years (range 20-89) and 49 (61%) patients were men. Median radiation dose was 59.5 Gy (range 16.2 -70 Gy). Pathology requiring replan included small cell lung cancer (n = 6, 8%), lung adenocarcinoma (n = 23, 29%), lung squamous cell carcinoma (n = 25, 31%), mesothelioma (n = 7, 9%), thymic malignancy (n = 5, 6%) or other histology (n = 10, 13%). 46 (58%) patients received concurrent systemic or chemotherapy. Six (8%) patients were treated in a BID approach. Histology, frequency of treatment, and concurrent systemic treatment were not significant predictors of patients requiring replan. Of the 80 total patients that required replanning, a total of 122 replans were completed. A total of 360 quality assurance CT (QACT) scans were used for all replans. Sixty (75%) patients required only one re-plan, 20 (25%) required two or more re-plans. Median number of treatments prior to the initial replan was 13 treatments (range 2 -41). Reason for requiring replanning included change in tumor size (n = 21), change in anatomy (n = 41, 51%), concern for toxicity (n = 4, 5%), change to radiation plan (n = 2, 3%), or technical/technique related changes (n = 12, 15%). CONCLUSION: Our single institution experience highlights the need for adaptive replanning in patients with thoracic malignancies treated with PBT to ensure adequate target coverage and to help spare normal tissue.

Molecular Status Predicts for Local Control in Patients with Non-Small Cell Lung Cancer Spinal Metastases Following Spine Stereotactic Body Radiotherapy.

PURPOSE/OBJECTIVE(S): We report outcomes after spine stereotactic body radiotherapy (SBRT) in patients with metastatic non-small cell lung cancer (NSCLC), to determine the significance of programmed death-ligand 1 (PD-L1) status and epidermal growth factor (EGFR) mutation on local failure (LF) rate. MATERIALS/METHODS: A total of 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary outcomes included overall survival (OS) and vertebral compression fracture (VCF) rates. OS was estimated using the Kaplan-Meier method. Cumulative LF and VCF rates were calculated using competing risk analysis method. Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: Median follow-up was 13 months (range, 0.5-95 months). Median OS was 18.4 months (95% CI 11.4-24.6). Median age was 67 years (range, 28.2-89.9). 52% were female, 76% had an adenocarcinoma histology and 61% had a smoking history. 49/165 (29%) had an EGFR mutation. PD-L1 status was analyzed in 109/165 (66%) patients with 16% PD-L1 ≥ 50%, 20% PD-L1 1-49% and 35% PD-L1 <1%. Of 389 segments, 79% were de novo and 21% were previously radiated. At baseline, 35% had a VCF, 27% had epidural disease, 27% had paraspinal extension, and 49% were Spinal Instability in Neoplasia Score (SINS) stable. 239/389 (61%) were treated with either 24 or 28 Gy in 2 SBRT fractions. Within 1 month of SBRT, 39/165 (24%) had a tyrosine kinase inhibitor, 27/165 (16%) immunotherapy (IO) with or without chemotherapy, and 31/165 (19%) chemotherapy alone. LF cumulative incidence at 1- and 2-years was 16.3% (95% CI 12.8-20.3%) and 25.4% (95% CI 20.9%-30%), respectively. EGFR positivity (p<0.0001), PD-L1≥50% (p = 0.013) and treatment with IO within 1 month of SBRT (p = 0.004) predicted for improved local control on MVA. The 1- and 2-year LF rate in EGFR-positive vs. negative patients were 12.9% vs. 16.6% and 17.7% vs. 28.8%, respectively, and in those PD-L1 ≥50% vs PD-L1<50% were 7.8% vs. 19.6% and 7.8% vs. 38.1% respectively. Cumulative incidence of VCF at 1- and 2-years were 6.6% (95% CI 4.4-9.4%) and 8.8% (95% CI 6.1-12.0%). MVA identified prior SBRT to the same treated segment (P<0.0001) and a baseline VCF (p<0.0001) as significant predictors. 18/389 (4.6%) had radiation-induced radiculopathy and no radiation myelopathy events detected. CONCLUSION: We identify the predictive utility of EGFR mutation and PD-L1 ≥50% status on local control in NSCLC patients with spinal metastases treated with spine SBRT, and a therapeutic benefit with peri-SBRT IO.

Stereotactic Body Radiotherapy for Posterior Element Only Spinal Metastases: Outcomes and Validation of Recommended Clinical Target Volume Delineation Practice.

PURPOSE/OBJECTIVE(S): Spine stereotactic body radiotherapy (SBRT) results in improved local control and pain response compared to conventional external beam radiotherapy. Consensus stipulates MRI-based delineation of the clinical target volume (CTV) is critical and is based on spine segment sector involvement. The applicability of these contouring guidelines to metastases confined to the posterior elements is unknown. The purpose of this study was to determine the patterns of failure, as well as the safety of treating posterior element metastases when the vertebral body was intentionally excluded from the CTV. MATERIALS/METHODS: A retrospective review of a prospectively maintained database of 605 patients and 1412 spine segments treated with spine SBRT was performed. Only treated segments involving the posterior elements alone were included for the analyses. The primary outcome was local failure, as per SPINO recommendations, and secondary outcomes included patterns of failure, toxicities. Clinical and tumor factors were reported with descriptive statistics. The cumulative risk of local failure was estimated using the Fine-Gray method, accounting for death before local failure as a competing risk. RESULTS: A total of 24/605 patients and 31/1412 segments within the database were treated to the posterior elements only. Local failure occurred in 11/31 segments. The cumulative rate of local recurrence was 9.7% at 12 months and 30.8% at 24 months. Amongst local failures, the most common histologies were renal cell carcinoma (36.4%) and non-small cell lung cancer (36.4%). At baseline, 4/11 (36.4%) segments with local failure (36.4%) had epidural disease and 8/11 (72.7%) had paraspinal disease. Most local failures were treated in the de novo setting (8/11, 72.7%). 6/11 (54.5%) failed exclusively within treated CTV sectors and 5/11 (45.5%) with both treated and adjacent untreated sectors. Of these five, four had disease progression within the untreated vertebral body. No failures occurred exclusively within the untreated vertebral body. One patient (4.2%) experienced a grade 4 skin toxicity and one patient (4.2%) developed an iatrogenic Grade 1 vertebral compression fracture. CONCLUSION: Posterior element alone metastases are rare. Our analyses support SBRT consensus contouring guidelines such that the vertebral body can be excluded from CTV in spinal metastases confined to the posterior elements.

[Study on the mechanism of early pancreatic exocrine function changes in severely scalded rats].

Objective: To explore the mechanism of early pancreatic exocrine function changes in severely scalded rats. Methods: The experimental research methods was used. Eighty male Sprague-Dawley rats aged 7-8 weeks were divided into simple sham injury group (n=8), sham injury+cholecystokinin octapeptide (CCK8) group (n=8), severe scald+CCK8 group (n=32), and extremely severe scald+CCK8 group (n=32) by the random number table, which were treated accordingly. Immediately after injury of rats in the 2 sham injury groups and 1, 2, 3, and 7 days after injury of rats in the 2 scald groups, the improved methods including pancreatic duct puncture and catheterization were used to dynamically collect the pancreatic-bile juice (PBJ) of rats. The PBJ secretory volume within 1 h was recorded, and the content of pancreatic lipase, α-amylase, and trypsin in PBJ was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 8. The femoral venous blood was collected, and the concentrations of pancreatic lipase and α-amylase in serum were detected by standard colorimetry to reflect their activity (n=8). The pancreatic tissue was extracted, and the levels of interleukin-1ß (IL-1ß) and IL-6 in pancreatic tissue were detected by ELISA (n=8), the expression of hypoxia-inducible factor 1α (HIF-1α) in pancreatic tissue was detected by immunofluorescence method, and the histopathological changes in pancreatic tissue were observed by hematoxylin-eosin staining, the severity of pancreatic tissue injury in the 2 scald groups was evaluated by modified Schmidt method (n=6), and the ultrastructure of acinar cells in pancreatic tissue was observed by transmission electron microscopy. Data were statistically analyzed with analysis of variance for factorial design, Tukey test, independent sample t test, and least significant difference test. Results: Compared with the PBJ secretory volume (0.740±0.030) mL in the pancreatic tissue of rats in simple sham injury group within 1 h immediately after injury, the (0.823±0.033) mL in sham injury+CCK8 group was significantly increased (t=4.92, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the PBJ secretory volume of rats within 1 h in severe scald+CCK8 group ((0.681±0.024), (0.608±0.056), (0.525±0.025), and (0.720±0.044) mL) and extremely severe scald+CCK8 group ((0.540±0.025), (0.406±0.021), (0.475±0.036), and (0.690±0.018) mL) was significantly decreased on 1, 2, 3, and 7 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the PBJ secretory volume of rats within 1 h in extremely severe scald+CCK8 group was significantly decreased on 1 and 2 days after injury (P<0.05). Compared with that of rats in simple sham injury group immediately after injury, the content of pancreatic lipase, α-amylase, and trypsin in PBJ of rats in sham injury+CCK8 group immediately after injury was significantly increased (with t values of 4.56, 3.30, and 4.99, respectively, P<0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the content of pancreatic lipase and α-amylase in PBJ of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group was significantly decreased on 1, 2, 3, and 7 days after injury (P<0.05), the trypsin content in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 2 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the content of pancreatic lipase in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 1, 2, and 3 days after injury (P<0.05), and the content of α-amylase and trypsin in PBJ was significantly decreased on 1 and 2 days after injury (P<0.05). There were no statistically significant differences in the activities of pancreatic lipase and α-amylase in serum of rats among the 4 groups at various time points after injury (P>0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the levels of IL-1ß in pancreatic tissue of rats in severe scald+CCK8 group on 1, 2, and 3 days after injury and in extremely severe scald+CCK8 group on 1, 2, 3, and 7 days after injury were significantly increased (P<0.05), and the levels of IL-6 in pancreatic tissue of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group were significantly increased on 1, 2, 3, and 7 days after injury (P<0.05). Compared with that in severe scald+CCK8 group, the IL-1ß level in pancreatic tissue of rats in extremely severe scald+CCK8 group was significantly increased on 2 and 3 days after injury (P<0.05), and IL-6 level in pancreatic tissue was significantly increased on 2 days after injury (P<0.05). The expression levels of HIF-1α in pancreatic tissue of rats in simple sham injury group and sham injury+CCK8 group immediately after injury were lower; and compared with that in sham injury+CCK8 group immediately after injury, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups increased to a certain extent at different time points after injury, and the expression position was transited from the edge of the pancreatic tissue to the whole pancreas, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups tended to be normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the proportion of acinar cell cytoplasm in pancreatic tissue of rats in sham injury+CCK8 group was increased; and with the increase of time after injury, edema, hemorrhage, necrosis, and inflammatory infiltration appeared in pancreatic tissue of rats in the 2 scald groups. Compared with that in severe scald+CCK8 group, the scores of edema, inflammatory cell infiltration, bleeding, and necrosis in pancreatic tissue of rats in extremely severe scald+CCK8 group were increased to varying degrees at various time points after injury, and the scores of pancreatic tissue of rats in the 2 scald groups basically recovered to normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the number of enzyme granules in acinar cells of pancreatic tissue of rats in sham injury+CCK8 group was increased, and with the increase of time after injury, the enzyme granules in acinar cells of rats in the 2 scald groups were gradually reduced basically. Conclusions: The exocrine functions of pancreas, such as synthesis and secretion of pancreatic enzymes, are decreased in the early stage in severely scalded rats. And the greater the scalded area, the more significant the decline of pancreatic exocrine function. This change may be related to hypoxic injury and inflammation in pancreatic tissue after severe scald.

[Clinical and genetic analysis of tyrosine hydroxylase deficiency of six cases].

The clinical and molecular genetic data of 6 patients with genetically confirmed tyrosine hydroxylase deficiency(THD) diagnosed in Department of Neurology, Qilu Hospital of Shandong University from March 2017 to February 2022 were retrospectively collected and analyzed. The 6 patients were from 5 families. Among them, 5 patients had persistent or paroxysmal abnormal walking posture, 4 patients had dystonia of head and face, including spasm of perioral and oculopharyngeal muscles, hyperactivity, and binocular upvision, 4 patients showed obvious morning light and evening heavy phenomenon, 2 patients had postural tremor of limbs, 2 patients had psychomotor retardation from childhood, 1 patient only had limb and cervical muscle weakness, 1 patient had epileptic seizures. Of the 6 patients, only 1 was adult-onset, and the rest were child-onset. Four patients had good response to low-dose dopa preparation, 2 patients from the same family had poor response to dopamine treatment, requiring extremely low dose initiation and multi-frequency titration treatment. However, the long-term treatment effect was poor with obvious abnormalities. Gene testing of 5 families revealed 8 mutations in the TH gene, with c.698G>A (p.R233H) being the hot spot mutation site. The clinical manifestations of THD are complex. Besides paroxysmal or persistent dystonia, it can also be accompanied by eye movement crisis, muscle weakness, epilepsy, and delayed mental and motor development. Most patients respond well to low-dose dopamine preparations, but a small number of patients require titration treatment with extremely low-dose dopamine preparations, and the long-term effect is not satisfactory.

[Investigation and analysis of clinical application of stainless steel crowns for primary molars in 2013 and 2022].

Objective: To provide references for the clinical popularization of stainless steel crowns by analyzing the clinical application and affecting factors of stainless steel crowns used in primary molars based on a questionnaire survey. Methods: Pediatric dentists from all over the country in June to December 2013 and June to December 2022 were selected to answer the survey questionnaire through the online or offline methods for analyzing the clinical application and influencing factors of stainless steel crowns used in primary molars. Results: A total of 712 and 580 questionnaires were distributed, and 608 and 512 valid questionnaires were recovered respectively in 2013 and 2022. The effective rates of the questionnaires were 85.4% and 88.3%. Among them, the usage rates of stainless steel crowns in 2013 and 2022 were 52.6% (320/608) and 78.1% (400/512) respectively, with a statistically significant difference (χ2=78.68, P<0.001). The main reasons for not selecting stainless steel crowns in 2013 were high technical sensitivity [52.8% (152/288)], followed by the impact of crown edge on gingiva [50.0% (144/288)] and poor aesthetics [27.8% (80/288)], while in 2022 were the inadequate equipage in hospitals [53.6% (60/112)] and poor aesthetics [21.4% (24/112)]. The main reasons for choosing stainless steel crowns restoration were good protection effect, less tooth fracture [78.1% (250/320) in 2013 and 82.5% (330/400) in 2022], followed by low dropout rate [62.5% (200/320) in 2013 and 68.0% (272/400) in 2022]. The proportions of stainless steel crowns restoration for primary molars after root canal therapy were 51.3% (312/608) and 76.6% (392/512) respectively with statistically significant (χ2=75.88, P<0.001). The proportions after pulp capping treatment for deep caries were 13.2% (80/608) and 53.1% (272/512) respectively, and the difference was statistically significant (χ2=206.01,P<0.001). Conclusions: During the 10 years from 2013 to 2022, the technical sensitivity of stainless steel crowns had gradually decreased, and the application in China had gradually increased. However, some hospitals have not yet equipped, which limits the application of stainless steel crowns. Therefore, training efforts should be derived to promote the clinical popularization of stainless steel crowns.

[Association between cognitive function and probability of prodromal Parkinson's disease in middle aged and elderly people aged 55 years and above in 4 provinces in China].

Objective: To analyze probability of prodromal Parkinson's disease (pPD) and assess the association between global cognitive function and cognitive domain function and probability of pPD in ≥55 years old middle-aged and elderly people in Hebei, Zhejiang, Shaanxi and Hunan Provinces in China. Methods: Data were collected from dataset of the Community-based Cohort Study on Nervous System Disease 2020. We selected 4 634 Alzheimer disease and Parkinson's disease free persons aged ≥55 years with completed information on demographics, disease history, cognitive test, and risk factors of Parkinson's disease for this study. Cognitive function was assessed using Montreal Cognitive Assessment Scale (Chinese version). Calculation of probability of pPD and assessment of possible/probable pPD were performed according to the criteria published by the International Parkinson and Movement Disorder Society. Multivariate linear regression model was used to analyze the association between cognitive function and probability of pPD. Results: The M (Q1,Q3) of global cognitive function and cognitive domains in terms of memory, execution, visuospatial function, language, attention and orientation were 25 (20, 30), 13 (11, 15), 10 (7, 12), 6 (4, 7), 5 (4, 6), 15 (12, 18) and 6 (6, 6) points, respectively. The M(Q1,Q3) of probability of pPD was 0.42% (0.80%, 1.73%), and the proportion of the study subjects with possible/probable pPD was 0.4%. Differences in the distribution of probability of pPD were significant among groups by total cognitive score quartiles (P<0.001), and the difference in proportions of study subjects with possible/probable pPD was significant and showed decline trend (P=0.001). After adjusted for confounders, the results of multivariate linear regression analyses showed that probability of pPD in the Q2, Q3 and Q4 group decreased by 23.4%, 31.2% and 20.1% compared with Q1 group, and corresponding ß values were 0.766 (95%CI: 0.702-0.836), 0.688 (95%CI: 0.631-0.751) and 0.799 (95%CI: 0.730-0.875), respectively, the trend was significant (P<0.001). Higher index scores of execution, visuospatial function, language, attention and orientation were highly related to lower probability of pPD (P<0.001). Conclusion: Declines in global cognitive function and cognitive domains of execution, visuospatial function, language, attention and orientation might increase the probability of pPD in middle-aged and elderly people, suggesting the importance of cognitive intervention in early stage for pPD prevention.

[Analysis of distribution characteristics of specific immunoglobulin E in 8 092 children with eczema and urticaria in a hospital of pediatric in Tianjin City].

To investigate the common specific immunoglobulin E(sIgE) in children with eczema and urticaria, compare the allergies in children with different diseases, genders and ages, and provide the scientific basis for the prevention, diagnosis and treatment. A retrospective study was conducted to analyze the children who were suspected of eczema and urticaria and tested for serum sIgE in the Tianjin Children's Hospital from December 2019 to August 2021. A total of 8 092 serum samples were tested for ten food allergens and ten inhaled allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes and ages and by the mass data. The results showed that the positive rate of eczema was 64.42%(5 213/8 092), and the urticaria was 35.58%(2 879/8 092). The positive rate of specific IgE was 66.65%(5 393/8 092), the food allergens was 61.74%(4 996/8 092), and the inhaled allergens was 34.85%(2 820/8 092). The top three positive rates of food allergens were egg 46.65%(3 775/8 092), milk 32.64%(2 641/8 092) and wheat flour 15.08%(1 220/8 092). The top three positive rates of inhaled allergens were house dust 21.40%(1 732/8 092), Alternaria 11.78%(953/8 092) and Dermatophagoides farinae 7.33%(593/8 092). The positivity of food allergens and inhaled allergens was significantly different in different age groups. The positive rates of food allergens in different age groups were 48.92%(947/1 936) in<1 year old, 72.28%(2 680/3 708) in 1-3 years old, 64.58%(919/1 423) in 4-6 years old and 43.90%(450/1 025) in>6 years old. The positive rates of inhaled allergens in different age groups were 17.67%(342/1 936) in<1 year old, 36.35%(1 348/3 708) in 1-3 years old, 46.38%(660/1 423) in 4-6 years old and 45.85%(470/1 025) in>6 years old. The top six positive rates of allergens of eczema were the same with urticaria, which were egg, milk, house dust, wheat flour, Alternaria and Dermatophagoides farinae. The allergens (greater than or equal to grade 4) differed in children with eczema and urticaria. Moreover, there were significant differences in the positive rates of Alternaria, egg, wheat flour, crab and shrimp. In conclusion, this study can reflect the epidemic characteristics of allergens in children with eczema and urticaria to a certain extent. There were significant differences in the positive rates of allergens between different age groups. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of allergic diseases.

[Perspectives on molecular diagnosis and targeted therapy for complex vascular malformations in pediatrics].

Vascular malformations are due to abnormal development of blood and/or lymphatic vessels during embryonic life without endothelial cell proliferation. Most of the previous treatments were symptomatic methods as surgery and sclerotherapy because the pathogenic mechanism was not clearly understood. With advances in molecular biology, the pathogenesis of vascular malformations is thought to be related to inherited and/or somatic mutations that eventually activate the PI3K/ATK/mTOR, Ras/Raf/MEK/ERK pathways. Also, related studies have promoted the use of targeted inhibitors. This article provides a review of current causative genes and targeted drugs for pediatric vascular malformations, aiming to provide a basis for promoting accurate molecular diagnosis and precision targeted therapy for these diseases.

[Progress in surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava].

Hepatocellular carcinoma(HCC) is one of the most common malignancies of the digestive system,which is prone to be associated with microvascular or macrovascular invasion. Among them,HCC with inferior vena cava tumor thrombus(IVCTT) or right atrium tumor thrombus(RATT) is rare and has a poor prognosis. However,surgical treatment of HCC with IVCTT and (or) RATT is rarely reported and summarized. The review described the classification of HCC tumor thrombus with IVCTT and (or) RATT, summarized the progress of surgical approaches and surgical operations,and introduced a case of thrombectomy after pushing from the outer surface of the atrium,rendering the RATT to the inferior vena cava under non-cardiopulmonary bypass. The review also proposed the prospective treatments for HCC with IVCTT or RATT,providing clinical guidance to hepatobiliary surgeons.

[The measurement and application of imaging evaluation parameters for cranio-cervical junction osseous and neural abnormalities:a review].

Cranio-cervical junction (CVJ) anomalies encompass a spectrum of bone,soft tissue,and neural structural abnormalities,including basilar invagination,platybasia,atlantoaxial dislocation,tonsillar herniation,and occipito-cervical fusion.Given the frequent coexistence of these anomalies and the intricate anatomical variations involved,precise imaging techniques and evaluation parameters are crucial for accurate disease characterization and treatment assessment.Since the 1930s,various parameters,such as the McRae line,Chamberlain line,Wackenheim line,and clivo-axial angle,have been widely employed for evaluating basilar invagination and platybasia.The advent of MRI and CT has further expanded the repertoire of parameters,including sagittal tilt,coronal tilt,medullary spinal angle,and intricate multi-axis evaluation systems.In this review,we summarize the relevant imaging parameters and their corresponding measurement techniques from previous literature,emphasizing high-sensitivity,consistent,and evidence-based parameters.This study aims to provide valuable insights for the imaging evaluation of CVJ anomalies.

[Advances in gene therapy of ocular surface and corneal diseases].

With the continual advancement of gene editing technology, gene therapy has been increasingly explored as a potential treatment option for both hereditary and acquired diseases. Due to its unique physiological and anatomical characteristics, the eye has emerged as an optimal target for gene therapy. In fact, ophthalmology was among the first clinical fields to obtain approval for in vivo gene therapy. Despite the widespread development of gene therapy targeting ocular surface and corneal diseases in recent years, a systematic review of these projects is still lacking. Thus, this review aims to comprehensively summarize the research progress and clinical application of gene therapy for ocular surface and corneal diseases, providing valuable guidance for future research and clinical translation.