Volume 104 · Issue 11 · 2024

The impact of human leukocyte antigen (HLA) on hematopoietic stem cell transplantation (HSCT) necessitates high precision in HLA genotyping. Confirmatory typing for patients and their related or unrelated donors before HSCT is critical. This study seeks to standardize HLA confirmatory typing in laboratories by examining the current state of HLA genotyping in the country, building upon the National Standards and Industrial Standards for HLA, and highlighting the significance of confirmatory typing for patients and potential donors prior to HSCT. A retrospective analysis over a decade reveals initial typing errors, indicating potential issues and critical considerations in pre-analytical, analytical, and post-analytical stages. Problems are attributed to three main causes: (1) random human errors, including technical mistakes, sample mix-up, and transcription inaccuracies; (2) limitations of technical methods, such as the varied sequence ranges between confirmatory and initial typing; (3) patient factors, involving high tumor burden, the influence of certain drugs on HLA genotyping results, and the second transplantation. Solutions are proposed for these problems, along with recommendations to standardize HLA confirmatory typing.

Micronutrients, including trace elements and vitamins, are essential nutrients in human metabolism. The majority of patients who need nutritional therapy have different levels of micronutrient deficiency for various reasons, which can lead to disease progression and affect clinical outcomes. In order to further standardize the application of micronutrients in medical nutrition therapy, nearly 100 experts in related fields were organized by the Chinese Society of Parenteral and Enteral Nutrition (CSPEN) to elaborate on the role and dosage of micronutrients based on the existing evidence-based medical evidence in common clinical conditions such as severe illness, surgery, burns, inflammatory bowel disease, short bowel disease, malignant tumors, chronic liver and kidney disease, elderly comorbidity, weight loss and chronic infection. Finally, 13 questions and 30 recommendations were put forward to provide reference for clinical standard application of parenteral and enteral nutrition in adult patients.

Dystrophinopathy refers to a group of X-linked recessive myopathies that primarily affect skeletal and/or cardiac muscle caused by pathogenic variants in the dystrophin-encoding DMD gene, including Duchenne muscular dystrophy, Becker muscular dystrophy, and X-linked dilated cardiomyopathy. The broad and complex spectrum of pathogenic DMD variants complicates the diagnosis and clinical classification in some patients. The precise genetic diagnosis is of great significance for the clinical diagnosis and treatment, multidisciplinary management, genetic counseling, prenatal diagnosis, and selection of gene therapy in dystrophinopathy. The present guideline is primarily based on the research advances in dystrophinopathy. Meanwhile, the foreign and domestic clinical guidelines or consensus for dystrophinopathy were referenced to put forward 18 recommendations and reach a consensus on the clinical manifestations, genetic basis, clinical diagnosis and classification, genetic diagnosis, and clinical genetic counseling of dystrophinopathy. This guideline aims to standardize and optimize the diagnostic process and reduce the diagnostic difficulty of patients with dystrophinopathy. In addition, this guideline provides some practical reference for clinicians and government staff.

To establish prediction models for human leukocyte antigen (HLA) haplotypes and HLA genotypes, and verify the prediction accuracy.

The prediction models were established based on the characteristic of HLA haplotype inheritance and linkage disequilibrium (LD), as well as the invention patents and software copyrights obtained. The models include algorithm and reference databases such as HLA A-C-B-DRB1-DQB1 high-resolution haplotypes database, B-C and DRB1-DQB1 LD database, G group alleles table, and NMDP Code alleles table. The prediction algorithm involves data processing, comparison with reference data, filtering results, probability calculation and ranking, confidence degree estimation, and output of prediction results. The accuracy of the predictions was verified by comparing them with the correct results, and the relationship between prediction accuracy and the probability distribution and confidence degree of the predicted results was analyzed.

The HLA haplotypes and genotypes prediction models were established. The prediction algorithm included the prediction of A-C-B-DRB1-DQB1 haplotypes according to HLA-A, B, DRB1, C, DQB1 genotypes, the prediction of C and DQB1 high-resolution results according to A, B and DRB1 high-resolution results, and the prediction of A, B, DRB1, C and DQB1 high resolution results according to the A, B and DRB1 intermediate or low resolution results. Validation results of "Predicting A-C-B-DRB1-DQB1 haplotypes basing on HLA-A, B, DRB1, C, DQB1 genotypes" model: for 787 data, the accuracy was 94.0% (740/787) with 740 correct predictions, 34 incorrect predictions, and 13 instances with no predicted results. For 847 data, the accuracy was 100% (847/847). The 2 411 and 2 594 haplotype combinations predicted from 787 and 847 data were grouped according to confidence degree, the accuracy was 100% (48/48, 114/114) for a confidence degree of 1, 96.2% (303/315) and 97.8% (409/418) for a confidence degree of 2 respectively. Validation results of "Predicting A, B, DRB1 and C, DQB1 high-resolution genotypes basing on HLA-A, B, DRB1 high, intermediate, or low resolution genotypes" model: when predicting C and DQB1 high resolution genotypes basing on A, B, and DRB1 high resolution genotypes, 89.3% (1 459/1 634) of the predictions were correct. The accuracy for the top 2 predicted probability (GPP) ranking was 79.2% (1 156/1 459), and for the top 10, it was 95.0% (1 386/1 459). Furthermore, when GPP≥90% and GPP 50%-90%, the prediction accuracy was 81.3% (209/257) and 72.8% (447/614) respectively. The accuracy of predicting C and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 high resolution genotypes from the China Marrow Donor Program was 87.0% (20/23). The accuracy of predicting A, B, DRB1, C, and DQB1 high resolution genotypes basing on the results of A, B, and DRB1 intermediate or low-resolution genotypes was 70.0% (7/10) and 52.5% (21/40) respectively. When predicting whether the patient is likely to have a HLA 10/10 matched donor, the accuracy of the top 2 GPP combinations with a proportion of ≥50% was 85.7% (6/7).

When using A, B, DRB1, C, DQB1 genotypes to predict A-C-B-DRB1-DQB1 haplotype combinations, the results with a confidence degree of 1 and 2 are reliable. When predicting C and DQB1 genotypes according to A, B and DRB1 genotypes, the top 10 results ranked by GPP are reliable, and the top 2 results with GPP≥50% are more reliable.

To investigate the effects of sirolimus combined with anti-CD20 monoclonal antibody desensitization on the prognosis of patients with haploidentical stem cell transplantation (haplo-SCT).

Fifteen consecutive patients who received haplo-SCT and pre-transplant donor specific anti-human leukocyte antigen (HLA) antibody (DSA) positive [mean fluorescence intensity (MFI)≥2 000] in the Institute of Hematological Diseases from November 2021 to March 2023 were retrospectively recruited into the desensitized group. There were 4 males and 11 females, with a median age [M(Q₁, Q₃)] of 48 (37, 59) years. All patients were desensitized with sirolimus combined with anti-CD20 monoclonal antibody. The non-desensitized group included 29 patients with haplo-SCT who had not received desensitization treatment from August 2012 to June 2016. There were 12 males and 17 females with a median age of 42 (26, 50) years. Up to October 1, 2023, the median follow-up time was 13 (9, 18) months in the study group and 23 (14, 29) months in the control group. The changes of MFI before and after desensitization treatment and the prognosis of patients in the desensitized group were compared, including the incidence of primary implantation failure (pGF), neutrophil implantation time, platelet implantation time, grade Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) and chronic GVHD incidence, non-recurrence related mortality, event-free survival rate, disease-free survival rate and overall survival rate. The survival curve was drawn by Kaplan-Meier method, and the survival rate between groups was compared with Log-rank test.

After desensitization treatment, the level of DSA MFI in the desensitized group decreased from 8 879 (7 544, 11 495) to 3 781 (1 638, 4 165) after desensitization treatment (P<0.01). All of the patients achieved hematopoietic recovery, and the median time for neutrophil and platelet engraftment were 14 (11, 15) and 20 (18, 25) days, respectively. The incidence of pGF in the desensitized group was 0, which was lower than that in the non-desensitized group (34.5%, 10/29) (P=0.011). The expected 1-year disease-free survival rate and overall survival rate in the desensitized group were 100% (15/15) and 100% (15/15) respectively, while those in the non-desensitized group were 75.9% (22/29) and 75.9% (22/29) respectively, the difference was not statistically significant (both P>0.05). The one-year event-free survival rate in the desensitized group was expected to be 100% (15/15), which was higher than that in the non-desensitized group (51.3%, 15/29) (P=0.002).

Sirolimus combined with anti-CD20 monoclonal antibody desensitization therapy can reduce the DSA level of haplo-SCT recipients, promote hematopoietic engraftment after transplantation, and avoid the occurrence of pGF after transplantation.

To evaluate the risk prediction and assessment function of HLA-DPB1 T-cell epitope (TCE) model and expression model in human leukocyte antigen (HLA)-matched unrelated hematopoietic stem cell transplantation (MUD-HSCT) with HLA-DPB1 mismatching.

A total of 364 (182 pairs) potential MUD-HSCT donors and recipients confirmed by HLA high-resolution typing in Shaanxi Blood Center from 2016 to 2019 were analyzed retrospectively. Of the 182 recipients, there were 121 males and 61 females with an average age of (26.3±14.2) years. Of the 182 donors, there were 148 males and 34 females with an average age of (33.7±7.5) years. Polymerase chain reaction-sequence-based typing (PCR-SBT), next-generation sequencing (NGS) and polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSO) based on LABScan^®3D platform were used for high-resolution typing of HLA-A, B, C, DRB1, DQB1, DPB1 gene, and PCR-SBT was used for single nucleotide polymorphism (SNP) typing. TCE model and expression model were used to predict and evaluate the HLA-DPB1 mismatch pattern and acute graft-versus-host-disease (aGVHD) risk.

A total of 26 HLA-DPB1 alleles and their 3′-UTR rs9277534 SNP genotypes were detected in this study population, and two new alleles HLA-DPB1*1052∶01 and HLA-DPB1*1119∶01 were found and officially named. The overall mismatch rate of HLA-DPB1 in MUD-HSCT donors and recipients was 90.66% (165/182). In TCE model, the HLA-DPB1 mismatch rates of permissible mismatch (PM) and non-permissible mismatch (non-PM) were 47.80% (87/182) and 42.86% (78/182), respectively. The non-PM in GvH direction was 13.73% (25/182), and which in HvG direction was 29.12% (53/182). A total of 73 pairs of donors and recipients in TCE model met the evaluation criteria of expression model. Among of TCE PM group, recipient DP5 mismatches accounted for 34.25% (25/73) were predicted as aGVHD high risk according to expression model. For the TCE non-PM group, both the recipient DP2 mismatches of 6.85% (5/73) and recipient DP5 mismatches of 10.86% (8/73) were predicted to be at high risk for aGVHD. Risk prediction by TCE model and expression model was 27.27% concordant and 16.97% unconcordant.

TCE model and expression model are effective tools to predict aGVHD risk of MUD-HSCT. Comprehensive application of the two models is helpful to the hierarchical assessment of HSCT risk.

To establish the threshold value of human leukocyte antigen (HLA) mixed antigen reagent screening test results, and to verify it by HLA single antigen reagent confirmation test results.

The results of 2 255 serum samples tested for HLA antibodies by HLA mixed antigen reagent in the department of HLA Laboratory, the First Affiliated Hospital of Soochow University from October 2017 to December 2021 were retrospectively analyzed. Among them, 1 139 samples were also tested by single antigen HLA Class-Ⅰ reagent and 1 116 samples were also tested by single antigen HLA Class-Ⅱ reagent. Based on the same antigens coated with both reagents, the Mean Fluorescence Intensity (MFI) and Nomalized Background ratio (NBG ratio) of 12 HLA Class-Ⅰ beads and 5 HLA Class-Ⅱ beads in the HLA mixed antigen reagent and the MFI of 77 anti-HLA class-Ⅰ antibodies and 35 anti-HLA class-Ⅱ antibodies detected by HLA single antigen reagent were recorded. The MFI and NBG ratio of HLA mixed antigen reagent beads in 1 139 or 1 116 samples were segmented according to the positive rate of antibodyies detected by the single antigen reagent corresponding to the antigens coated with each HLA mixed antigen reagent bead, and the results of the HLA mixed antigen screening test were verified by the HLA single antigen reagent confirmation test.

The threshold values of MFI and NBG ratio of HLA mixed antigen reagent′s 17 beads were established. The MFI of No. 1 to No. 17 beads of HLA mixed antigen reagent ranged from 26.86 to 21 925.58, and the NBG ratio ranged from 0 to 434.65. According to the positive detection rate of HLA single antigen reagent corresponding to the coated antigens, the MFI and NBG ratio of the beads of HLA mixed antigen reagent were divided into positive interval, suspicious positive interval, suspicious negative interval and negative interval. The positive rates of anti-HLA class-Ⅰ antibodies by HLA mixed antigen reagent and single antigen HLA Class-Ⅰ reagent were 87.5% (997/1 139) and 66.3% (755/1 139). The positive rates of anti-HLA class-Ⅱ antibodies were 63.4% (707/1 116) and 44.9% (501/1 116). In the samples with suspicious negative, suspicious positive and positive results of HLA class-Ⅰ、Ⅱ antibodies detected by HLA mixed antigen reagent, the positive detection rates of single antigen HLA Class-Ⅰ reagent were 14.9% (17/114), 41.3% (145/351) and 91.3% (590/646), respectively. The positive detection rates of single antigen HLA Class-Ⅱ reagent were 15.5% (58/375), 26.5% (81/306) and 88.8% (356/401), respectively.

In this study, the threshold values of MFI and NBG ratio of HLA mixed antigen reagent screening test are established, and the threshold values are verified by the results of HLA single antigen reagent confirmation test. HLA mixed reagent screening test can be used for screening of HLA antibodies, and if necessary, it should be combined with HLA single antigen confirmatory test for clinical detection of HLA antibodies.

To analyze the transfusion effect of different platelet matching schemes in patients with platelet transfusion refractoriness (PTR).

A total of 94 patients with PTR received by Taiyuan Blood Center from January to December 2021 were retrospectively analyzed, including 26 males and 68 females, aged 53(34,66) years. Platelet antibody screening was performed by enzyme-linked immunosorbent assay (ELISA). For patients with positive human leukocyte antigen (HLA) class Ⅰ antibodies, Luminex platform liquid chip assay was used to identify the specificity of antibodies, and platelets with missing allelic expression antigen corresponding to their specific antibodies were found in the platelet donor gene database established in our laboratory. For patients with negative class HLA-Ⅰ antibody screening, medium and high-resolution HLA-A and B alleles were genotyped by polymerase chain reaction restriction sequence specific oligonucleotide (PCR-SSO), and the compatible platelets were searched from the platelet donor gene database by HLA cross-reactive group genotype matching scheme or directly selected by serological cross-matching. The PCI compliance rate and total transfusion effective rate of different mismatch site groups and different matching scheme groups were statistically analyzed.

Platelet antibody was detected in 39 of 94 PTR patients with a positive rate of 41.5%, and all of them were HLA-Ⅰ antibodies, and 1 case was accompanied by human platelet antigen (HPA) antibody. A total of 134 times of compatible platelets were supplied to 39 patients with HLA-Ⅰ antibody positive by using antibody avoidance matching method. And the total effective rate of transfusion was 97.8% (131/134); The PCI compliance rates of HLA-A antigen mismatch, HLA-B antigen mismatch and HLA-A and B antigen mismatch groups were 81.6% (31/38), 86.5% (32/37) and 78.6% (22/28), respectively. The total effective rate of transfusion was 97.4% (37/38), 94.6% (35/37) and 100% (28/28), respectively, with no statistical significance (all P>0.05). A total of 118 times of compatible platelets were provided by HLA antigen cross-reaction group genotype matching and serological cross-matching, 90 transfusion effects were collected during follow-up, and the total effective rate was 76.7% (69/90).

The combination of different platelet matching schemes can improve the PCI compliance rate and the total effective rate of transfusion in PTR patients.

To conduct a comparative study of radiological and clinical outcomes between percutaneous transfacet screw (TFS) and pedicle screw (BPS) in oblique lateral lumbar interbody fusion (OLIF) for single-level lumbar spinal stenosis.

A retrospective cohort study. Patients who underwent OLIF with TFS or BPS for the treatment of single-level lumbar spinal stenosis at Beijing Jishuitan Hospital from January 2019 to June 2022 were retrospectively analyzed. Radiological parameters and clinical indicators were compared between the two groups. Radiological parameters included preoperative, immediate postoperative (within 5 days), and 1-year postoperative measurements of disc height and segmental lordosis angle, as well as interbody fusion status at 1 year postoperatively. Clinical indicators included operative time, blood loss, length of hospital stay, complications, and Oswestry Disability Index (ODI), visual analogue scale (VAS) scores for back pain, and leg pain before and 1 year after surgery.

Four male and 10 female patients with an average age of (61.0±11.2) years underwent OLIF with TFS, while 9 male and 12 female patients underwent OLIF with BPS, with a mean age of (60.9±6.7) years. There was no statistically significant difference in preoperative disc height between the TFS and BPS groups (P>0.05). The immediate postoperative disc height was (12.9±2.1) mm and it was (10.4±1.7) mm at 1-year follow-up in the TFS group; in the BPS group, it was (12.9±2.1) mm immediately postoperatively and (11.9±2.1) mm at 1-year follow-up; there was statistically significant difference between the two groups at 1-year follow-up (P=0.037). The segmental lordosis angle showed no significant differences within each group or between the two groups at preoperative, immediate postoperative, or 1-year postoperative follow-up (all P>0.05). At 1-year postoperative follow-up, the fusion rates was 92.9%(13/14) in the TFS group and 95.2%(20/21) in the BPS group, with no statistically significant difference between the two groups (P>0.05). The TFS group had a significantly shorter operative time and less blood loss compared to the BPS group [(164.3±33.9) minutes vs (191.7±31.8) minutes and (74.3±46.9) ml vs (124.8±54.0) ml, respectively] (both P<0.05). Both groups showed significant improvement in ODI and VAS scores at 1 year postoperatively compared to those preoperatively, but with no statistically significant difference was found between the groups (both P>0.05).

OLIF with TFS fixation can effectively restore disc height and alleviate back and leg pain in patients with single-level lumbar spinal stenosis. Compared to the OLIF with BPS procedure, OLIF with TFS has shorter operative time and less blood loss.

To investigate the effect of plasminogen activator urokinase receptor (PLAUR) gene on neutrophil activation and apoptosis in neutrophil-like cell model.

Human acute myeloid leukemia cell line HL60 was cultured in vitro and induced to differentiate into neutrophil-like cells by all-trans retinoic acid (ATRA). Lentiviral vectors interfering with human PLAUR gene was constructed and transfected into neutrophil-like cells (siRNA group). The phosphate buffer saline (PBS) group (untransfected neutrophil-like cells) and normal blank control group (NC group) (neutrophil-like cells transfected with blank plasmid) were used as controls (n=3). After starvation culture and addition of interleukin-17 afterwards in these 3 groups, the expression of CD11b on the cell membrane was detected by flow cytometry, and the levels of myeloperoxide (MPO) and extracellular neutrophil traps (NETs) in the supernatant were detected by enzyme-linked immunosorbent assay (ELISA) to investigate the activation of neutrophil-like cells. The apoptosis was detected by flow cytometry with annexin V/propidium iodide (PI) double staining and the expressions of apoptosis-related proteins caspase-3, bax and bcl-2 were detected by Western blotting.

The expression of CD11b in siRNA group (32.37±8.17) was lower than that in PBS group (46.27±1.54) and NC group (53.07±8.14) (P<0.05) by flow cytometry. The levels of MPO and NETs (33.37±1.11, 57.69±3.03) in the supernatant of siRNA group were significantly lower than those in PBS group (41.64±2.20, 77.60±4.33) and NC group (40.84±5.11, 76.15±2.10) (P<0.05). Flow cytometry with annexin V/PI showed that the expression of apoptosis in siRNA group (20.42%±2.45%) was significantly higher than that in PBS group (11.91%±2.23%) and NC group (11.13%±2.56%) (P<0.05). The relative expression of caspase-3 protein and bax protein (0.84±0.05, 0.83±0.04) in siRNA group was significantly higher than that in PBS group (0.68±0.02, 0.63±0.08) and NC group (0.71±0.01, 0.66±0.10) (P<0.05), and the relative expression of anti-apoptosis protein bcl-2 decreased in siRNA group (0.38±0.02) than in PBS group (0.73±0.05) and NC group (0.69±0.06) (P<0.05).

PLAUR promotes the activation of neutrophil-like cells and inhibits the apoptosis.

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that　HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient′s HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K.　Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

Ischemic stroke is one of the common clinical diseases. Most patients often see the doctor with symptoms of neurological deficit such as unclear speech, unilateral limb weakness, skewed mouth angle, hemianopia, etc. Headache is easily masked by other impressive clinical manifestations. In recent years, although there have been clear diagnostic criteria and classification of headache caused by ischemic stroke, the clinical characteristics of pain still lack reliable description and are often missed. At present, the pathogenesis of acute headache originating from ischemic stroke includes several possible theories, but there is no unified conclusion. There are few studies on the treatment of headache, lack of high-quality randomized controlled studies, and more dependence on empirical treatment in clinical practice. This article focuses on the epidemiology, pathological mechanism, risk factors, clinical characteristics and prognosis of acute headache in ischemic stroke.

The skin, an important component of the body's physical barrier and susceptible to injury and pathogens, is innervated by dorsal root ganglion (DRG) sensory neurons that receive mechanical, thermal, and chemical stimuli, which include harmful signals that cause itching or pain. Microorganisms that colonize the skin play a key role in tissue homeostasis and maintenance of physiological functions. Among them, Staphylococcus aureus is an opportunistic infection pathogen and the main cause of bacterial infection in humans. However, the role of pathogenic microorganisms in driving pruritus is unknown. In order to study the role of Staphylococcus aureus in pruritus, the research team used a mouse model of percutaneous exposure associated with specific dermatitis. In this model, the researchers topically inoculated S. aureus on depilated back skin and closed it with tape during bacterial exposure, causing rupture and inflammation of the epidermis at the inoculation site. Finally, it was found that after the skin of mice was exposed to S. aureus, the inflammation score increased significantly, the scratching behavior also increased significantly, and the skin damage even spread beyond the original exposed site. In addition, filament contact with this harmless stimulus usually does not cause itching, but the research team found that mice exposed to Staphylococcus aureus group caused itching under filament stimulation. This phenomenon of abnormally sensitive skin is called itch dissimilation.

The incidence of KRAS G12C gene mutation in patients with metastatic colorectal cancer is 3% to 4%, and it is associated with poor prognosis of patients. For patients whose initial treatment with fluorouracil-based chemotherapy with or without bevacizumab was ineffective, standard post-line treatment with trifluridine tepipirimidine tablets (Tas-102) or regorafenib had limited efficacy, with an objective response rate of only 1% to 2%, a median progression-free survival of ≤2 months, and at the expense of adverse drug reactions. Currently, no targeted therapy driven by positive selection biomarkers has been approved for the treatment of KRAS-mutated colorectal cancer patients. Sotoracib is a small molecule inhibitor targeting KRAS G12C mutant protein, which can selectively and irreversibly inhibit KRAS G12C protein to block downstream proliferation and survival signaling pathways. The team's early research showed that sotolasib monotherapy has limited efficacy in colorectal cancer, but its combination with panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be an effective method. Therefore, the team designed the CodeBreaK 300 study.

Parkinson's disease (PD) and related dementia is one of the fastest-growing neurological diseases in the world, and one of its pathological mechanisms is the accumulation of alpha-synuclein in fragile neurons in the brain. Prolonged life span, genetic factors, and long-term exposure to the associated environment are suspected to be the main drivers of PD risk and progression. Plastic pollution from plastic production and waste deposition worldwide has become one of the most pressing environmental threats facing the world, leading to microplastic pollutants in water and food. Microplastics refer to the diameter<5 mm particles, including smaller nanoplastics (<1 μ m). Disposable polystyrene products, such as disposable takeaway tableware, can generate large amounts of polystyrene waste, resulting in widespread plastic pollution. These nanoplastic contaminants promote the formation and propagation of α-synuclein fibers through high-affinity interactions with two domains (amphipathic and non-amyloid component) in α-synuclein.