With the continuous development and maturity of anti-tumor immunotherapy technology,im-mune checkpoint inhibitors as one of the main methods of immunotherapy were increasingly widely used in clinical tumor cases,bringing new hope for many advanced cancer patients with poor response to tradi-tional treatment,but at the same time,reported on adverse reactions of various organs related to this were also increasing,and the immune damage caused by them was harmful to patients,especially immune checkpoint inhibitor-associated pneumonia,immune checkpoint inhibitor-associated myocarditis and im-mune checkpoint inhibitor-associated encephalitis,which could even seriously endangered the lives of pa-tients.Therefore,it was necessary for clinicians to fully understand and master the mechanism,clinical characteristics,laboratory and imaging examination characteristics,diagnostic criteria and differential di-agnosis conditions,and treatment principles of adverse reactions that may be caused by immune check-point inhibitors,so as to find a more optimized anti-tumor treatment regimen and actively prepared for the treatment of possible immune-related adverse reactions.In this paper,we reported a case of immune checkpoint inhibitor-associated severe pneumonia,referred to the relevant guidelines,introduced its clinical features,laboratory and imaging findings,difficulties encountered in the diagnosis and treatment process,briefly analyzed the causes,and reviewed the possibility of immune-related pneumonia should be considered when respiratory symptoms occurred in patients receiving immunotherapy;the increased ratio of blood neutrophil count to lymphocyte count,and the increased ratio of eosinophil count to lymphocyte count could be used as indicators to indicate immune-related adverse reactions in patients;bronchoalveo-lar lavage fluid examination and bronchoscopy and lung biopsy were helpful for the diagnosis;when im-mune checkpoint inhibitor-associated severe pneumonia occurred,in addition to symptomatic and sup-portive treatment,adequate glucocorticoid-based immunosuppressive therapy should be given in time,and combined with cytokines monoclonal antibodies and other biological agents,immunoglobulin co-therapy,but the current indications for the use of biological agents were not fully clear,and the use of high-dose immunosuppressive drugs might cause the risk of severe infection.Therefore,according to the relevant literature and the findings in the process of clinical diagnosis and treatment,this paper proposed that the serum levels of IL-6,TNF-α,CRP and other inflammatory mediators in patients may be used as a quantitative indication to initiate biological agent therapy and accumulate experience for better solving similar problems in the future.

Objective:To investigate the diagnostic and prognostic value of 68Ga-fibroblast activation protein inhibitor (FAPI) PET for hepatobiliary malignancies. Methods:From July 2020 to February 2023, 33 patients (23 males, 10 females; age (55.4±13.5) years) with suspected or confirmed liver or biliary tract malignancies who underwent 68Ga-FAPI PET in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed. PET images were evaluated by 3 experienced nuclear medicine physicians, and the results of biopsy or postoperative pathology, clinical and imaging follow-up were used as the gold standard. One-way analysis of variance and least significant difference t test were used to compare the differences among groups. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. Results:Of 33 patients, 14 performed PET for initial diagnosis and staging, and 19 for restaging. There were 14 patients with hepatocellular carcinoma (HCC), 13 patients with cholangiocarcinoma (CCA), and 6 patients with gallbladder carcinoma (GBC). The primary tumor of HCC, CCA and GBC all showed significant 68Ga-FAPI uptake, with no statistically significant difference in SUV max among groups ( F=1.58, P=0.250). The sensitivities of 68Ga-FAPI PET for initial diagnosis and restaging of hepatobiliary malignancies were 14/14 and 15/15, respectively. Compared with conventional imaging, 68Ga-FAPI PET changed the diagnosis and staging in 29.2%(7/24) patients. The treatment strategy was changed in 30.3%(10/33) patients with malignant tumors due to 68Ga-FAPI PET findings. Follow-up showed 22 cases survived and 11 cases died, with the overall survival of 355.56(80.00, 516.97) d, and 1- and 2-year survival rates were 68.2% and 57.9%, respectively. Semi-quantitative 68Ga-FAPI PET parameters such as SUV max, target-liver ratio (TLR), and target-blood ratio (TBR) had no significant prognostic value, but the prognosis of the group without distant metastases diagnosed by 68Ga-FAPI PET was significantly better than that of the group with distant metastasis ( P=0.032). Conclusion:68Ga-FAPI PET has high sensitivity for the diagnosis of hepatobiliary malignancies, which can help guide treatment decisions and prognosis evaluation.

Objective:To investigate the influencing factors for endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events in novice trainees and establishment of its prediction model.Methods:The prospective study was conducted. The clinical data of 12 novice trainees of ERCP in the First Hospital of Lanzhou University from July 2016 to July 2019 were selected. The operation was performed by 12 novice trainees of ERCP under the guidance of the endoscopic experts. Observation indicators: (1) ERCP-related adverse events in novice trainees; (2) analysis of influencing factors for ERCP-related adverse events in novice trainees; (3) establishment of a prediction model for ERCP-related adverse events in novice trainees. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed by the t test. Measurement data with skewed distribution were represented as M(range), and com-parison between groups was analyzed by the Mann-Whitney U test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed by the chi-square test. The Logistic regression model was used for univariate and multivariate analyses. The regression coefficients were used to construct a prediction model. The receiver operating characteristic curve was drawn, and the area under curve was used to evaluate the predictive ability. Results:(1) ERCP-related adverse events in novice trainees. Of the 300 patients with ERCP operated by 12 novice trainees, 52 cases had ERCP-related adverse events and 248 cases had no ERCP-related adverse events. Cases in grade 1?2 or grade 3?4 of ERCP difficulty classification, score for intubation time, score for cannulation time, cases with or without completion of the cannulation, cases with or with-out basket stone removal, cases with or without stenosis expansion, score for contrast-enhanced interpretation, score for implementation of reasonable treatment and score for expected purpose reached were 22, 30, 8(range, 5?10), 20(rang, 9?20), 24, 28, 11, 41, 0, 52, 39±17, 39±19 and 44±23 for novice trainees with ERCP-related adverse events, versus 146, 102, 6(range, 4?9), 12(range, 8?20), 163, 85, 94, 154, 20, 228, 52±22, 80±20, 52±23 for novice trainees without ERCP-related adverse events, showing significant differences in the above indicators between them ( χ2=4.79, Z=?2.46, ?2.72, χ2=7.01, 5.30, 4.49, t=?4.00, ?2.97, ?2.29, P<0.05). (2) Analysis of influencing factors for ERCP-related adverse events in novice trainees. Results of univariate analysis showed that the diffi-culty classification of ERCP, intubation time, cannulation time, completion of cannulation, basket stone extraction, contrast-enhanced interpretation, implementation of reasonable treatment and expected purpose reached were related factors for ERCP-related adverse events in novice trainees ( odds ratio=1.95, 1.11, 1.08, 0.45, 0.44, 0.97, 0.98, 0.98, 95% confidence intervals as 1.07?3.58, 1.02?1.22, 1.02?1.14, 0.24?0.82, 0.22?0.90, 0.96?0.99, 0.96?0.99, 0.97?1.00, P<0.05). Results of multi-variate analysis showed that difficulty classification of ERCP and contrast-enhanced interpretation were independent influencing factors for ERCP-related adverse events in novice trainees ( odds ratio=2.08, 0.95, 95% confidence intervals as 1.10?3.96, 0.92?0.99, P<0.05). (3) Establishment of a predic-tion model for ERCP-related adverse events in novice trainees. According to the important outcome indicators of clinical training and results of multivariate analysis, 4 indicators including difficulty classification of ERCP, intubation time, cannulation time and contrast-enhanced interpretation were included to establish a prediction model for ERCP-related adverse events in novice trainees, which indicated that trainees with the predicted score >0.4 were in high risk of ERCP-related adverse events. The area under receiver operating characteristic curve of the prediction model was 0.72(95% confidence interval as 0.65?0.79, P<0.05), with the best cut-off value as 0.40, the sensitivity as 76.9% and the specificity as 63.3%. Conclusion:The difficulty classification of ERCP and contrast-enhanced interpretation are independent influencing factors for ERCP-related adverse events in novice trainees. Novice trainees with a predicted score >0.4 are high-risk groups of ERCP-related adverse events.

Objective:To explore the application of "upgraded single-entry colonoscope training method" in the primary endoscopic training of refresher doctors.Methods:A total of 71 refresher doctors who participated in the primary single endoscopy training in the Endoscopy Center of the Affiliated Hospital of Qingdao University from January 2017 to December 2019 were randomized to two groups: upgraded single-entry endoscopy training group ( n=36) and traditional single-entry endoscopy training group ( n=35). In the first week of training, all the participants learned the basic theory of single-entry enteroscopy insertion. From week 2 to week 11, each doctors of the two groups finally completed 80 to 100 cases of single-entry endoscopy. The upgraded single-entry colonoscopy training group was divided into two stages: "rectum-proximal sigmoid colon" and "descending colon-ileocecal part" with the boundary of descending-sigmoid colon as the dividing point, which was different from the traditional group. At the 12th week, each doctors were assessed by 20 cases of single-entry colonoscopy operation. the success rate of ileocecum insertion, the time to pass through sigmoid colon, the rate of loop formation and the average operation time of successful ileocecum insertion were compared between the two groups. SPSS 26.0 was used for t test or chi-square test. Results:Compared with the traditional single-entry endoscopy training group, the upgraded single-entry endoscopy training group achieved better results in the successful rate of ileocecal insertion (66.8% vs. 59.0%, P=0.005), the time to pass sigmoid colon [(6.05±3.32) min vs. (7.15±3.12) min, P<0.001], the loop rate (35.13% vs. 40.71%, P=0.035), the average operation time of successfully inserting the ileocecal part [(9.01±2.12) min vs. (10.25±3.12) min, P<0.001] and the discomfort response score [(5.19±1.41) vs. (6.70±2.15), P<0.001], with statistical significance between the groups. Conclusion:"Upgraded single-entry endoscopy training method" emphasizes no loop through sigmoid colon, which is more helpful for refresher doctors to master the operation skills of single-entry colonoscopy, shorten the teaching time, and reduce the discomfort of patients, and is suitable for popularization in the teaching.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To establish and evaluate acute hepatic sinusoidal obstruction syndrome (HSOS) mouse models induced by three pyrrolidine alkaloids (PAs) including monocrotaline (MCT), retrorsine (RTS) and senecionine (SEN).Methods:Forty-eight male C57 mice were divided into four groups, control group, MCT group, RTS group and SEN group, with 12 mice in each group, which were gavaged once with phosphate buffer saline (300 μL), MCT solution (800 mg/kg), RTS solution (100 mg/kg) and SEN solution (100 mg/kg), respectively. At 24 hours after gavage, the number of mortality and success modeling, liver function, and pathological changes of liver of four groups of mice were analyzed. One way analysis of variance, Bonferroni test and Chi-square test were used for statistical analysis.Results:At 24 hours after gavage, the number of dead mice of MCT group, RTS group and SEN group was zero, nine and zero, respectively; and the number of survival successfully modeled mice was nine, three and six, respectively; the difference of mortality among three groups was statistically significant ( χ2=21.734, P<0.05), and the difference of the number of success modeling was not statistically significant ( χ2=2.836, P>0.05). The alanine aminotransferase (ALT) levels of MCT group, RTS group and SEN group were (111.72±37.62), (562.97±242.42) and (3 891.40±1 009.44) U/L, respectively; aspartate transaminase (AST) levels were (156.96±64.95), (331.22±120.83) and (2 107.55±532.80) U/L, respectively; and total bilirubin (TBil) levels were (41.66±10.42), (79.43±18.45) and (120.80±17.44) μmol/L, respectively, which were all higher than those of the control group ((31.40±10.98) U/L, (34.66±13.00) U/L and (16.91±2.89) μmol/L, respectively); and the differences were statistically significant (Bonferroni test, all P<0.008 3). There were statistically significant differences in ALT and AST levels between MCT group and RTS group (Bonferroni test, both P<0.008 3), while there was no statistically significant difference in TBil level between two groups ( P>0.008 3). There was statistically significant difference in TBil level between MCT group and SEN group (Bonferroni test, P=0.002), however there were no statistically significant differences in ALT and AST levels between two groups (both P>0.008 3). There were statistically significant differences in ALT, AST and TBil levels between RTS group and SEN group (Bonferroni test, all P<0.008 3). The mouse liver tissues of all three groups showed coagulative necrosis of hepatocytes, subendothelial hemorrhage of central vein, the dilation of hepatic sinusoids, erythrocyte clogging in the space of disse, and destruction of normal lobular structure. In MCT and RTS groups, the main damages were hepatocyte necrosis, sinusoidal dilatation and congestion in zone 3 of the liver acinus, while in SEN group, which were hepatocyte necrosis and sinusoidal congestion in zone 1 and 2 of the liver acinus. The histological changes of mouse liver tissues of MCT group were moderate to severe, and those of RTS group and SEN group were all severe. Conclusions:Acute HSOS mouse models induced by three kinds of PA including MCT, RTS and SEN are successfully established, of which MCT is the most suifable choice.

Objective To investigate the clinical effects of Shenlian capsule,trastuzumab combined with SOX regimen in the treatment for HER-2 positive advanced gastric carcinoma.Methods A total of 314 patients with HER-2 positive advanced gastric carcinoma in our hospital were randomly divided observation group and control group,157 cases in each group.The observation group was treated by SOX regimen and trastuzumab,while the control group was given Shenlian capsule on the base of control group.After treatment,the short-term effects in the 2 groups were evaluated.Before and after the treatment,the levels of SDF-1,CXCR4,FSP-1 and MRP-l4 in the 2 groups were detected.During the treatment,the rates of neurotoxicity,gastrointestinal reaction,liver function injury,renal function injury,rashes and bone marrow suppression were observed in the 2 groups.After the treatment,3 years follow-up was performed,the 1 year survival rate,3 year survival rate,overall survival (OS) and progression-free survival (PFS) were observed.Results After the treatment,the control rate (92.7％ vs.79.9％;Z=3.812,P=0.037) and efficiency rate (78.1％ vs.66.4％;Z=3.712,P=0.039) were significantly higher in treatment group than which in the control group (P＜0.05).After the treatment,the levels of SDF-1,CXCR4,FSP-1,MRP-14 in treatment group were significantly lower than control group (t=4.091,4.310,3.972,3.821,P＜0.05).During the treatment,the rates of neurotoxicity,gastrointestinal reaction,liver function injury,renal function injury,rashes,bone marrow suppression were significantly lower in treatment group than control group (x2=5.182,4.671,4.491,5.091,5.204,4.925,P＜0.05 or P＜0.01).After the treatment,the PFS,OS (t=3.714,3.612,P＜0.05),3 year survival rate (x2=3.105,P=0.043) were significantly higher in treatment group than the control group.Conclusions The Shenlian capsule,trastuzumab combined with SOX regimen has a good effect and low toxic effects in the treatment of HER-2 positive advanced gastric carcinoma,and they could prolong the survival time.

Objective To evaluate the effect rotation constancy static magnetic field(RCSMF) on the expression of bone morphogenetic protein-2 (BMP-2) and platelet-derived growth factors (PDGFs) in fracture healing, and elucidate the possible mechanism of RCSMF promoting fracture healing.Methods A total of 80 rats with femur closed fracture were randomly divided into a magnetic treatment group (M) and a control group (C).The M group was given RCSMF treatment 30 minutes per day, 6 times per week, using 0.4 T 6 Hz magnetic field, while the C group was not given any intervention.Femurs and calluses were subjected to BMP-2, PDGF-A and PDGF-B immunohistochemistry assay at 2, 3, 4 and 8 weeks after the treatment.The integrated optical density (IOD) of positive staining was calculated.Two-factor variance analysis was used to compare the main effect of time, treatment and that of their interaction.Results For both groups, the IOD of immunoreactivity of BMP-2 at 2, 3 and 4 weeks after the treatment was significantly higher than that 8 weeks after the treatment, and the value at four weeks after the intervention was also significantly higher than that at 2 weeks after it.There was a significant interaction effect of time × treatment of BMP-2 (F =3.17, P ＜ 0.05).Significant differences were observed in the IOD of positive staining PDGF-A at different time points for both groups : the value at 2 weeks after treatment was significantly higher than that at 3, 4 and 8 weeks after the treatment, and that at 3 and 4 weeks after treatment was also significantly higher than that at 8 weeks after the treatment.The IOD of positive staining PDGF-B of the M group (57.6 ± 2.1) was significantly higher than that of the C group (50.11 ± 2.22, P ＜ 0.05).There was significant difference in the IOD of positive staining PDGF-B (F =50.06 ,P ＜ 0.01) at different time points : the IOD of positive staining PDGF-B at 3 weeks after treatment was significantly higher than that at 2 and 8 weeks group after the treatment, and the value at 2 and 4 weeks after treatment was also significantly higher that at 8 weeks after the treatment.Conclusion RCSMF may elevate the expression BMP-2 and PDGF-B to promote fracture healing.

Objective Toinvestigatetheriskfactorsforleukoaraiosis(LA)inpatientswithlarge arteryatherosclerosis(LAA).Methods Theclinicaldata(age,sex,hypertension,diabetes,smoking, serum lipid level,hyperhomocysteinemia,and numbers of stenosis or occluded cerebral arteries)of 312 patients with LAA classified by the modified stop stroke study trial of Org 10172 in acute stroke treatment (SSS-TOAST ) were analyzed retrospectively. The age-related white matter changes (age related white matter changes,ARWMC)scale was used to evaluate LA. All the 312 patients were divided into non-LA group(n=72)and LA group(n=240)according the T2 weighted magnetic resonance imaging (MRI) and fluid attenuated inversion recovery(FLAIR)sequence,and 3 groups according to the (age-related white matter changes,ARWMC)scores:mild LA,moderate LA,and severe LA groups. The patients with multiple risk factors were analyzed by the univariate and multivariate Logistic regression analyses. Results (1)Of the 312 patients with LA,227 were males (72. 8%). Their average age was 64 ± 11 years,and 240 of them (76. 9%)had LA. Multivariate Logistic regression analysis showed that age (OR,2. 911,95%CI 1. 647-5.146,P=0. 000),hypertension (OR,2. 583,95%CI 1. 373-4.857,P<0. 01),diabetes (OR,1. 882, 95%CI 1. 058-3. 348,P <0. 05),the numbers of stenosis or occlusion arteries (OR,1. 851,95%CI 1.018-3. 367,P<0. 05),and lacunar infarction (LI)(OR,1.493,95%CI 1. 202-1. 853,P<0. 01)were the risk factors for LA. (2)The comparison of the clinical data in patients with different severity in the LA group found that there were significant differences in age,hypertension,diabetes,the numbers of stenosis or occlusionarteries,andLIamongthe3groups(allP<0.05).Conclusion Age,hypertension,diabetes, the numbers of stenosis or occlusion arteries,and LI are the independent risk factors for patients with LAA,and it is associated with the severity of LA.

Objective To explore the effect of integrated rehabilitation on bed-ridden and complcations of the elderly. Methods 109bed-ridden inpatients who accepted rehabilitation were designed as rehabilitation group. 100 bed-ridden inpatients who did not accept rehabilitationwere randomly elected from all the inpatients at the same time were designed as the control group. Their bed-ridden rate, complications,and Modify Barthel Index (MBI) were compared. Results The MBI impoved, and the incidence of bed-ridden and complications reducedin the rehabilitation group compared with those in the control group (P=0.00) after treatment. Conclusion Integrated rehabilitationcan effectively reduce the bed-ridden rate and complications, and improve the activity of daily living of the elderly.