Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers.

Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types of cancer. However, the widespread use of ICIs has brought about a number of safety concerns, especially the development of immune-related adverse events (irAEs). These serious complications could result in treatment discontinuation and even life-threatening consequences, making it critical to identify high-risk groups and predictive markers of irAEs before initiating therapy. To this end, the current article examines several potential predictive markers of irAEs in important organs affected by ICIs. While retrospective studies have yielded some promising results, limitations such as small sample sizes, variable patient populations, and specific cancer types and ICIs studied make it difficult to generalize the findings. Therefore, prospective cohort studies and real-world investigations are needed to validate the potential of different biomarkers in predicting irAEs risk. Overall, identifying predictive markers of irAEs is a crucial step towards improving patient safety and enhancing the management of irAEs. With ongoing research efforts, it is hoped that more accurate and reliable biomarkers will be identified and incorporated into clinical practice to guide treatment decisions and prevent the development of irAEs in susceptible patients.

Isoalantolactone mediates the degradation of BCR-ABL protein in imatinib-resistant CML cells by down-regulating survivin.

Isoalantolactone (Iso) is a bioactive lactone isolated from the root of Inula helenium L, which has been reported to have many pharmacological effects. To investigate the role and mechanism of isoalantolactone in chronic myeloid leukemia (CML), we first investigated isoalantolactone's anti-proliferative effects on imatinib-sensitive and imatinib-resistant CML cells by CCK8. Flow cytometry was used to detect isoalantolactone-induced cell apoptosis. Survivin was overexpressed in KBM5 and KBM5T315I cells using the lentivirus vector pSIN-3×flag-PURO. In KBM5 and KBM5T315I cells, shRNA was used to knockdown survivin. Cellular Thermal Shift Assay (CETSA) was used to detect the interaction between isoalantolactone and survivin. The ubiquitin of survivin induced by isoalantolactone was detected through immunoprecipitation. Quantitative polymerase-chain reaction (Q-PCR) and western blotting were used to detect the levels of mRNA and protein. Isoalantolactone inhibits the proliferation and promotes apoptosis of imatinib-resistant CML cells. Although isoalantolactone inhibits the proteins of BCR-ABL and survivin, it cannot inhibit survivin and BCR-ABL mRNA levels. Simultaneously, it was shown that isoalantolactone can degrade survivin protein by increasing ubiquitination. It was demonstrated that isoalantolactone-induced survivin mediated downregulation of BCR-ABL protein. It was also revealed that isoalantolactone triggered BCR-ABL protein degradation via caspase-3. Altogether, isoalantolactone inhibits survivin through the ubiquitin proteasome pathway, and mediates BCR-ABL downregulation in a caspase-3 dependent manner. These data suggest that isoalantolactone is a natural compound, which can be used as a potential drug to treat TKI-resistant CML.

Prognostic role of ring finger and WD repeat domain 3 and immune cell infiltration in hepatocellular carcinoma.

We have found that the expression of ring finger and WD repeat domain 3 (RFWD3) is significantly higher in unpaired and paired hepatocellular carcinoma (HCC) tissues than in normal tissues. Moreover, this expression has a significant correlation with the infiltration level of 14 immune cell types and when the detected RFWD3 expression levels were grouped as high and low, a prominent difference was revealed for overall survival, disease-specific survival, and progression-free interval. Through statistical analysis (univariate Cox), we were also able to identify RFWD3 as an independent prognostic element for HCC, with RFWD3 having an ability to accurately predict HCC prognosis (area under the curve of 0.863). Finally, we have generated prognostic nomograms for probabilities of 1-, 3- and 5-year overall survival in HCC via integrating the factors of age, pathologic stage, alpha-fetoprotein level, and RFWD3 expression.

Prognosis-related metabolic genes in the development of colorectal cancer progress and perspective.

Colorectal cancer (CRC) is one of the most commonplace malignant tumors in the world. The occurrence and development of CRC are involved in numerous events. Metabolic reprogramming is one of the hallmarks of cancer and is convoluted and associated with carcinogenesis. Lots of metabolic genes are involved in the occurrence and progression of CRC. Study methods combining tumor genomics and metabolomics are more likely to explore this field in depth. In this mini-review, we make the latest progress and future prospects into the different molecular mechanisms of seven prognosis-related metabolic genes, we screened out in previous research, involved in the occurrence and development of CRC.

Assessment of Radiation Shielding Requirements in Room of Radiotherapy Installations—Part 1: General Principle (GBZ/T 201.1—2007): A survey of relevant personnel in technical service institutions / 中国辐射卫生

Objective　 @#To evaluate the implementation, application, and problems and suggestions of the Radiation Shield- ing Requirements in Room of Radiotherapy Installations—Part 1: General Principle (GBZ/T 201.1—2007) through a survey of relevant personnel in radiation health technical service institutions, and to provide a scientific basis for further revision and implementation of this standard.@*Methods@#A questionnaire survey was conducted among randomly selected per- sonnel in radiation health technical services across China, which mainly investigated the awareness, training, application, and revision suggestions related to the GBZ/T 201.1—2007. The results were aggregated and analyzed.@*Results@#A total of 184 evaluation questionnaires on the GBZ/T 201.1—2007 were collected from technical service staff in 25 provinces. Among the responders, 64.1% thought that the standard had been widely applied; 91.8% thought that the standard could meet work needs; only 54.3% ever received relevant training on the standard; 68.5% used the standard once or more per year; 33.7% thought that the standard needed to be revised.@*Conclusion@#The personnel in radiation health technical services have a high awareness rate of the GBZ/T 201.1—2007 and its contents, but their familiarity with and application of the standard need to be improved. Relevant departments should strengthen the training and promotion of the standard, and part of the standard should be revised.

Core connotation of compatibility of Aconiti Lateralis Radix Praeparata-Glycyrrhizae Radix et Rhizoma herb pair under physiological/ pathological conditions based on metabolomics and network pharmacology / 中国中药杂志

This study aims to explore the core connotation of the compatibility of Aconiti Lateralis Radix Praeparata(Fuzi)-Glycyrrhizae Radix et Rhizoma(Gancao) herb pair under physiological and pathological conditions. The biochemical indicators of serum/myocardial tissue, pathological changes of the myocardial tissue, and serum metabolic profiles of normal rats and heart failure model rats treated with Fuzi Decoction and Fuzi Gancao Decoction were determined. Network pharmacology and metabolomics were employed to establish the metabolite-target-pathway network for Glycyrrhizae Radix et Rhizoma in enhancing the efficacy and reducing the toxicity of Aconiti Lateralis Radix Praeparata, Western blotting was employed to verify the representative pathways in the network. The results showed that both decoctions lowered the levels of creatine kinase and other indicators and mitigate myocardial pathological injury in model rats. However, they caused the abnormal rises in creatine kinase and other indicators and myocardial pathological injury in normal rats. The results indicated that the compatibility reduced the toxicity in normal rats and enhanced the efficacy in model rats. The results of metabolomics showed that Fuzi Gancao Decoction recovered more metabolites in model rats and had weaker effect on interfe-ring with the metabolites in normal rats than Fuzi Decoction. The association analysis showed that the network of Glycyrrhizae Radix et Rhizoma enhancing the efficacy of Aconiti Lateralis Radix Praeparata involved 112 metabolites, 89 targets, and 15 pathways, including calcium and cAMP signaling pathways. The network of Glycyrrhizae Radix et Rhizoma reducing the cardiotoxicity of Aconiti Lateralis Radix Praeparata involved 36 metabolites, 59 targets, and 11 pathways, including adrenergic signaling and tricarboxylic acid cycle in cardiomyocytes. The experimental results of protein expression verified the reliability of the association analysis. This study demonstrated that the core connotation of the herb pair of Aconiti Lateralis Radix Praeparata-Glycyrrhizae Radix et Rhizoma changed under physio-logical and pathological states, and the compatibility results of enhancing efficacy and reducing toxicity were achieved with different metabolic pathways and biological processes.

Results and analysis of intercomparison in the 2019—2021 national personal dose monitoring / 中国辐射卫生

@#<b>Objective</b> To analyze the process of intercomparison of national personal dose monitoring, evaluate the ability of personal dose monitoring, and ensure the accuracy and reliability of monitoring results in our laboratory. <b>Methods</b> In accordance with the intercomparison protocol for 2019—2021, an energy-discriminant thermoluminescence dosimeter was used for measurement at different doses. The uncertainty of measurement was evaluated and compared with the reference value. <b>Results</b> <i>H</i>_p(10) was measured for intercomparison in 2019—2021. In 2019, the single group performance difference was −0.02 to 0.02 and the comprehensive performance was 0.02. These values were 0.02-0.10 and 0.05 in 2020, and −0.02 to 0.02 and 0.01 in 2021. The intercomparison results were rated as excellent in the three consecutive years. <b>Conclusion</b> The personal dose monitoring system in our laboratory was in good condition, and the monitoring results were accurate and reliable. Improving the knowledge of personnel and cultivating a serious working attitude are important for intercomparison and personal dose monitoring.

Evaluation of delayed laparoscopic cholecystectomy after percutaneous transhepatic gallbladder drainage in the management of acute cholecystitis / 中华普通外科杂志

Objective:To evaluate delayed laparoscopic cholecystectomy (DLC) after percutaneous transhepatic gallbladder drainage (PTGBD) in acute cholecystitis.Methods:Clinical data of 64 patients who were diagnosed moderate (grade Ⅱ) acute cholecystitis by the 2018 Tokyo Guidelines in acute phase and underwent delayed LC at our hospital from Jan 2018 to Jan 2021 were compared between two groups ie PTGBD treatment (21 cases)in acute stage before DLC and DLC without PTGBD group (43 cases). The difficulty score of TG18 was used to evaluated every surgical procedure of the cases by reviewing the operation videos.Results:Patients in DLC after PTGBD group had a longer hospital stay and operation time, more blood lose and higher difficulty score than the DLC without PTGBD group(all P<0.05). There was no statistically significant difference in the conversion rate and morbidity rate between the two groups( P>0.05). Conclusion:This study fails to show there is any if ever benefit of PTGBD before DLC over DLC without PTGBD in the management of Grade Ⅱ acute cholecystitis.

The Role of Platelet Exosomes in Atherogenic Thrombosis --Review / 中国实验血液学杂志

Exosomes are subtypes of extracellur vesicles containing a variety of cell-specific proteins, lipids and nucleic acids released during cell activation or apoptosis, and play the role of intercellur communication mediators in different physiological and pathological processes. With the development of research in recent years, the role of platelet-derived exosomes in cardiovascular diseases has attracted extensive attention. This paper reviews the role of platelet-derived exosomes in atherosclerotic thrombosis and the potential role of platelet-derived exosomes as biomarkers for the diagnosis and treatment of atherosclerotic thrombotic disease and the problems to be solved.

Status quo of radiation protection in some pet hospitals in Beijing-Tianjin Region, China / 中国辐射卫生

Objective To analyze the status quo and existing problems of radiation protection for veterinary X-ray facilitiesin Beijing-Tianjin region, China, and to provide a basis for improving radiation protection management level. Methods According to the requirements of the Technical guidelines for status quo assessment of occupational hazard of the employing unit (AQ/T 4270—2015), the study performed status quo assessment on the workplaces of veterinary X-ray facilities in 16 pet hospitals in Beijing-Tianjin region, and comprehensively analyzed the impact of the workplaces on the health of radiation workers and the public. Results In terms of personnel management, the pass rates of occupational health management post setting, personnel training, personal protective equipment, individual monitoring of occupational external exposure, notification of occupational hazards, and occupational health surveillance were 100%, 81.3%, 100%, 75%, 37.5%, and 25%, respectively. In terms of workplace management, most workplaces had reasonable layout and zoning and complete protection and emergency devices. However, there were some problems in some places, such as non-standard radiation warning signs, no notice board of occupational hazards, and no radiation protection testing. In terms of document management, all institutions had imperfect system documents. Conclusion The workplaces of veterinary X-ray facilities in 16 institutions basically meet the requirements for radiation protection, but there are also some problems, such as inadequate management of personnel and workplace radiation protection, and imperfect system documents. Institutions should strengthen the study of radiation protection knowledge. The competent authorities should strengthen supervision, formulate corresponding standards for radiation protection, enhance training, and improve the professional level of staff.

Role of Acupuncture in Amblyopia Treatment.

CONTEXT: Amblyopia is an ophthalmological developmental disorder that occurs during early childhood due to disrupted binocular vision. It leads to reduced best-corrected visual acuity in one eye (seldom in both eyes) in which the visual acuity of one eye is 2 rows weaker than the other eye on a Snellen vision testing chart. Many studies have reported the outcomes of acupuncture in the treatment of amblyopia. Evidence suggests that acupuncture improves outcomes in children with amblyopia, but these studies are associated with several limitations which may affect the evaluation of the efficacy and reproducibility of studies on acupuncture. One important limitation is the lack of sham acupuncture as a control which has not been used in any clinical trial. The use of nonacupoint acupuncture is suggested as a placebo to improve the quality of evidence and comparability?

Current opinions on the mechanism, classification, imaging diagnosis and treatment of post-traumatic osteomyelitis / 中华创伤杂志(英文版)

Post-traumatic osteomyelitis (PTO) is a worldwide problem in the field of orthopaedic trauma. So far, there is no ideal treatment or consensus-based gold standard for its management. This paper reviews the representative literature focusing on PTO, mainly from the following four aspects: (1) the pathophysiological mechanism of PTO and the interaction mechanism between bacteria and the body, including fracture stress, different components of internal fixation devices, immune response, occurrence and development mechanisms of inflammation in PTO, as well as the occurrence and development mechanisms of PTO in skeletal system; (2) clinical classification, mainly the etiological classification, histological classification, anatomical classification and the newly proposed new classifications (a brief analysis of their scope and limitations); (3) imaging diagnosis, including non-invasive examination and invasive examination (this paper discusses their advantages and disadvantages respectively, and briefly compares the sensitivity and effectiveness of the current examinations); and (4) strategies, including antibiotic administration, surgical choices and other treatment programs. Based on the above-mentioned four aspects, we try to put forward some noteworthy sections, in order to make the existing opinions more specific.

Intracellular free heme concentration detection versus high-risk human papillomavirus detection in screening cervical cancer and precancerous lesions / 中国基层医药

Objective:To compare the application value of intracellular free heme concentration (FH) detection and high-risk human papillomavirus (HPV) detection in screening cervical cancer and precancerous lesions.Methods:A total of 238 patients with cervical abnormalities who received FH and HPV detection in Huainan First People's Hospital, China from October 2017 to October 2019 were included in this study. Taking liquid-based ThinPrep cytologic test (TCT) results and pathological biopsy results as gold standard, the diagnostic value of FH detection and TCT detection for cervical cancer and precancerous lesions were compared.Results:TCT results revealed normal/inflammatory diagnosis in 97 patients, and atypical squamous cells of undetermined significance (ASCUS) or higher grade diagnosis in 141 patients. Pathological biopsy results reported cervical intraepithelial neoplasia (CIN) grade II or above in 70 out of the 141 patients. The detection rate of FH detection for CIN grade II or above cervical lesions was 92.86% (65/70) and the detection rate of high-risk HPV detection was 95.71% (67/70). The sensitivity and specificity of FH detection in the screening CIN grade II or above cervical lesions were 82.86% (58/70) and 85.92% (60/70), respectively and they were 94.29% (66/70) and 98.59% (69/70) for high-risk HPV detection. There were significant differences in diagnostic sensitivity and specificity between FH dection and high-risk HPV detection ( χ2 = 4.52, 10.25, both P < 0.05). Conclusion:High-risk HPV detection is of high application value in the diagnosis of cervical cancer and precancerous lesions. It has higher sensitivty and specificity in screening cervical cancer and precancerous lesions than FH detection. But FH detection is simpler, more economical and easier to use and is more suitable for large-scale screening of cervical cancer and precancerous lesions than high-risk HPV detection.

Expression and Clinical Significance of Heat Shock Protein 90 in Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression of HSP90 in bone marrow samples of multiple myeloma (MM) patients and explore its clinical significance.@*METHODS@#Maxvision immunohistochemistry technique was used to detect the protein expression level of HSP90 76 MM patients and 29 normal healthy donors. The clinical characteristics of the patients were collected, and the correlation between the HSP90 expression and the clinical characteristics was analyzed.@*RESULTS@#The count of MM patients with positive HSP90 protein was significantly higher than that of normal healthy donor, and there were no significant correlation between HSP90 expression and age, sex, hemoglobin (Hb), creatinine (CREA), blood calcium, lactate dehydrogenase (LDH), bone marrow plasma cell proportion and MM subtypes (P>0.05), but HSP90 expression was correlated with β@*CONCLUSION@#HSP90 protein was over-expressed in MM patients, and was correlated with β

Arthroscopic classification and management for the popliteal hiatus of the lateral meniscus tears / 北京大学学报(医学版)

OBJECTIVE@#To bring forward an arthroscopic classification of the popliteal hiatus of the lateral meniscus (PHLM) tears and to assess the effects of arthroscopic all-inside repair with suture hook in management of such injuries.@*METHODS@#This study involved 146 patients who underwent arthroscopic operation because of PHLM tears from April 2014 to October 2017, eliminating the patients who had discoid lateral meniscus. There were 81 males and 65 females, with 54 left knees and 92 right knees. The average ages were (34.7±3.7) years. Among the selected participants, there were 107 patients with anterior cruciate ligament (ACL) injuries, 39 patients with medial collateral ligament (MCL) injuries, and 48 patients with medial meniscus tears. The average preoperative Lysholm and International Knee Documentation Committee (IKDC) scores were 57.7±9.2 and 54.1±8.9, respectively. The arthroscopic classification was based on the extent and degree of PHLM tears and using the arthroscopic all-inside repair with suture hook for such injuries. For the patients associated with ACL injuries, the ipsilateral autograft hamstring tendons use as the reconstruction graft for single bundle ACL reconstructions. The suture anchors were used for treatment of MCL Ⅲ injuries, and the arthroscopic all-inside repair for medial meniscus tears.@*RESULTS@#A total of 146 PHLM tears in 146 patients were divided into type Ⅰ (tears not involved in popliteus tendon incisura; n=86, 58.9%), type Ⅱ (tears involved in popliteomeniscal fascicles; n=36, 24.7%), and type Ⅲ (tears involved in popliteus tendon incisura; n=24, 16.4%). For type Ⅰ, there were three subtypes, including type Ⅰa: longitudinal tear (n=53, 61.6%), type Ⅰb: horizontal tear (n=27, 31.4%), and type Ⅰc: radial tear (n=6, 7.0%). For type Ⅱ, there were also three subtypes, including type Ⅱa: anterosuperior popliteomeniscal fascicle tear (n=5, 13.9%), type Ⅱb: posterosuperior popliteomeniscal fascicle tear (n=20, 55.6%), and type Ⅱc: both tears (n=11, 30.6%). For type Ⅲ, there were two subtypes, including type Ⅲa: horizontal tear (n=9, 37.5%), type Ⅲb: radial tear (n=15, 62.5%). In the follow-up for an average of 15.3±2.6 months, all the patients had done well with significantly improved Lysholm (84.6±14.3) and IKDC (83.2±12.8) scores at the end of the last follow-up relative to preoperative scores (P > 0.01).@*CONCLUSION@#We propose that it is possible to classify lateral meniscus tears at the popliteal hiatus region for three types, which can summarize the injury characteristics of this area. The arthroscopic all-inside repair with suture hook for the PHLM tears can avoid stitching to popliteal tendon or narrowing popliteal hiatus and have satisfactory clinical results.

Analysis of radioactive occupational hazard evaluation results of some medical institution construction in Tianjin / 中国辐射卫生

Objective To evaluate the current status of radioactive occupational hazards in the construction of some medical institutions in Tianjin, discover existingproblems and deficiencies, and provide a technical basis for radiation protection management. Methods Based on the requirements of relevant regulations and standards, we comprehensivelyevaluated the results of the pre-evaluation and control effect evaluation of 81 radioactive occupational hazards in Tianjin. Results Among the 35 proposed protective measures for pre-evaluation of radiation occupational hazards constructionprojects, the lowest compliance rate is warning signs and personal protective equipment. Among the 46 construction projects of radioactive occupational hazard control evaluation, the pass rate of protective measures was between 73.9% and 100%, with the lowest pass rate for personal protective equipment. Besides, the pass rate of radiation protectionmanagement evaluation was 95.7% ～ 100%, with the lowest pass rate for the protection management system.The initial inspectionpass rateof the equipment quality control acceptancewas 98.6%, while the pass rate was 97.1% for the relevant workplace radiation protection during the initial inspection. Conclusion The pre-evaluation completion rate of radiological occupational hazard evaluation in Tianjin medical institution construction project, unilateral and area of construction room, workplace layout and zoning, ventilation, shielding measures, personal dose management and occupational health inspection all meet the requirements of regulations and standards. However, there are still some deficiencies in the personal protective equipment, warning signs and the radiation protection management system. Therefore, the regulatory department should further strengthen the evaluation of medical institutions, especially the key supervision and management of non-conformities.

Desmoplakin and clinical manifestations of desmoplakin cardiomyopathy / 中华医学杂志(英文版)

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.