Immune checkpoint inhibitors (ICIs) have been approved for the treatment of urothelial carcinoma(UC). However, the use of antibiotics, proton pump inhibitors, corticosteroids, beta-blockers, metformin, and statin concomitant medications in some patients due to complications during the treatment process may affect the clinical efficacy of ICIs through different pathway, making it difficult for patients to derive clinical benefit or making it more likely to develop drug resistance. In this paper, we present a review of the effects of the above concomitant drugs on ICIs in the treatment of patients with advanced UC, with a view to provide reference for the application of individualized treatment strategies of ICIs in patients with advanced UC.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVE To establish the method for content determination of related substances in Oxcarbazepine tablets. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted and the separation was performed on ZORBAX Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate solution （pH6.0） （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was 230 nm and column temperature was set at 35 ℃. The sample size was 10 μL. RESULTS The linear ranges of oxcarbazepine and impurity A， B， C， D， E， I， K， L and N were 0.192-1.440， 1.019-7.639， 0.208-1.559， 0.230-1.727， 0.389-2.915， 0.182-1.364， 0.393-2.945， 0.199-1.493， 0.199-1.490 and 0.200- 1.503 μg/mL， respectively （all r＞0.999）. The detection limits were 0.046， 0.037， 0.049， 0.027， 0.077， 0.040， 0.114， 0.054， 0.055 and 0.039 μg/mL. The quantitation limits were 0.152， 0.122， 0.162， 0.090， 0.258， 0.132， 0.380， 0.181， 0.185 and 0.130 μg/mL. RSDs of precision， repeatability， stability （24 h） and durability tests were all lower than 5.0%. The average recoveries were 92.8%-105.6% （RSD≤3.0%， n＝9）. Only impurity K and unknown impurity were detected in the original preparation sample， with a total content of 0.078% to 0.083%； impurities A， B， D， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅰ， with a total content of 0.147% to 0.163%； impurities A， B， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅱ， with a total content of 0.085% to 0.161%. CONCLUSIONS The established method is rapid， sensitive， accurate， stable and durable. It can be used for the content determination of 9 known impurities in Oxcarbazepine tablets.

OBJECTIVE To establish a reciprocating tube dissolution method to investigate the similarity of in vitro dissolution behavior of oxcarbazepine scored tablet preparations between the original and generic drugs, and to evaluate the differences in dose-specific pharmaceutical properties between the original and generic drugs. METHODS Using 250 mL of pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer, and water(all 0.5% sodium dodecyl sulfate) as the dissolution medium, and reciprocating frequency of 10 dip min-1, using a reciprocating tube dissolution device to determine the dissolution curves of generic drugs and original research drugs, and combining the similarity factor(f2) method to evaluate the similarity of dissolution behavior between generic drugs and original research drugs, and compared the result with paddle method. The friability, weight variation and loss of mass of half-tablets were determined by friability tester and electronic balance through splitting by hand and by the cutting device respectively. RESULTS The f2 of generic drug A in 4 dissolution medium were higher than 50 and showed its similarity to original drug. While the generic drug B was not consistent with the dissolution behavior of original drug as its f2 factorswere all less than 50 in 4 dissolution. The post-segmentation weight variation, loss of mass and fragility of generic drug A and B were higher than those of the original drug. CONCLUSION The dissolution curve of oxcarbazepine half tablet preparation measured by the reciprocating cylinder method has good discrimination compared to the paddle method, and there is still a certain gap in the quality control of the generic drug in different doses compared to the original research drug.

Objective:To study the clinical, imaging and pathological features of duodenal gangliocytic paraganglioma (DGP).Methods:The clinical, imaging and pathological data of patients with DGP treated at the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2012 to October 2021 were retrospectively analyzed.Results:Of 8 patients with DGP, there were 7 males and 1 female, with a median age of 52 years (range 37 to 57 years). Five patients were asymptomatic and they were diagnosed on physical examination followed by investigations. Three patients presented with black stools. CT examination showed localized nodular thickening of the duodenum, with enhanced scanning showing obvious progressive contrast enhancement. Endoscopic ultrasonography showed a hypoechoic submucosal lesion in duodenal wall. Histologically, the neoplasm composed of three different cell types which included Schwann cells, epithelioid cells, and ganglioid cells. The Schwann cells expressed NF, NSE and S-100 proteins; the epithelioid cells expressed CK, NSE, Syn and CgA proteins; while the ganglioid cells expressed NSE, Syn, CgA and NF proteins. Endoscopic submucosal dissection was performed in 2 patients and surgical resection was performed in 6 patients.Conclusion:DGP is a rare benign neurogenic tumor which is most commonly found in the duodenum. It has a good prognosis. Imaging and endoscopic examinations demonstrated a submucosal mass. The main treatment are endoscopic resection and local surgical resection.

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.

Objective:To investigate the clinical characteristics, skeletal muscle pathologies and gene variations of chronic progressive external ophthalmoplegia (CPEO).Methods:Sixteen patients with conformed CPEO, admitted to our hospital from January 1997 to December 2021, were chosen. Their clinical data such as onset age and course of diseases and muscle pathological examination results were collected and their gene variation characteristics were analyzed.Results:The initial symptom in all 16 patients was ptosis of varying degrees; 15 patients were with eye movement disorder, 6 with diplopia, 4 with proximal limb weakness, and 3 with dysphagia and dysarthria. Among the 16 patients, electromyography showed myogenic damage in 7 patients, myogenic combined with neurogenic damage in 1 patient, neurogenic damage in 1 patient, and normal in 7 patients. Skeletal muscle biopsies indicated that 14 patients were with ragged red fibers (RRF), 11 patients had cytochrome C oxidase (COX)-negative muscle fibers, 3 patients had a small amount of degenerated and necrotic myofibers with mononuclear phagocytic infiltration. Immunohistochemical staining indicated infiltration of CD8 and CD68 positive lymphocytes. Ten patients accepted genetic test, indicating 6 patients with single large fragment deletion of mitochondrial DNA (mtDNA), 1 patient with mtDNA point mutation, 1 patient with nucleosomal DNA (nDNA) point mutation, and 2 patients without pathogenicity variation clearly associated with clinical phenotype. Electron microscopy in 5 patients showed that abnormal mitochondrial aggregation was noted in 4 patients under the sarcolemma and among the myofibrils.Conclusion:In addition to ptosis and eye movement disorders, a small number of patients with CPEO may be accompanied by dysphagia and limb weakness; and single large fragment deletion of mtDNA is the main mutation form of CPEO.

Developmental coordination disorder (DCD) is a childhood-onset condition that primarily affects physical co-ordination.In China, DCD is not well recognized and is under-treated.Knowledge of the evaluation and intervention of DCD among physiotherapists (PT) is limited.In 2020, the Academy of Pediatric Physical Therapy of the American Physical Therapy Association published the Physical Therapy Management of Children with Developmental Coordination Disorder: An Evidence-Based Clinical Practice Guideline.From the perspective of PT, this review aims to make a comprehensive interpretation of the recommendations in the guideline regarding the physical examination and evaluation, physiotherapy planning and implementation, and family education of children at risk or diagnosed with DCD.This article aims to make DCD get more attention from domestic PT through the interpretation of the latest guidelines, and strengthen the knowledge of physiotherapy assessment and management in children with DCD to guide the clinical practice.

Objective:To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome.Methods:Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing.Results:The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing.Conclusions:High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.

Objective:To evaluate the value of next generation sequencing (NGS) in the genetic testing of Lynch syndrome.Methods:Immunohistochemical method was used to detect the expressions of DNA mismatch repair (MMR) proteins, including MutL homolog 1 (MLH1), PMS1 homolog 2 (PMS2), MutS homolog 2 (MSH2) and MutS homolog 6 (MSH6) in colorectal cancer, gastric cancer and endometrial cancer tissues collected from Shandong Provincial Hospital between 2016 and 2018. The genomic DNA of 45 patients who were suspected with Lynch syndrome was extracted from non-cancerous tissue paraffin samples, which were postoperatively confirmed by microscope. The mutations of 12 genes including MLH1 and MSH2 were detected using NGS. The germline mutant sites and significance were analyzed by bioinformatics technology and further confirmed by using Sanger sequencing.Results:The immunohistochemical results showed that the 45 cases of suspected Lynch syndrome included 22 cases of MLH1 and PMS2 deficient expression, 16 cases of MLH2 and MSH6 deficient expression, and 7 cases of MMR proteins normal expression. The NGS result showed that 28 cases of adjacent sample from colon cancer patients included 4 cases of MLH1 pathogenic mutation, 1 case of suspected MLH1 mutation, 2 cases of MLH2 pathogenic mutation, 2 cases of suspected MLH2 mutation. No MMR gene mutation was found in adjacent samples of 6 cases of rectal cancer, 6 cases of gastric cancer and 7 cases of colorectal cancer with MMR normal expression. One case of MLH1 or MHL2 pathogenic mutation and one case of MLH1 suspected mutation was detected in adjacent samples of 5 cases of endometrial cancer. Moreover, NGS also detected many other genes mutations and unreported gene mutation sites. Pathogenic and suspected MLH1 and MSH2 mutations were verified by Sanger sequencing.Conclusions:High-throughput NGS is a quick, accurate and reliable technique to identify gene variants in suspected Lynch syndrome patients. It has a wide application prospect for gene testing of tumors associated with Lynch syndrome.