OBJECTIVE To provide reference for rational clinical use of immune checkpoint inhibitor （ICI）. METHODS Electronic medical record information of patients who received ICI treatment from January 1st 2020 to December 31st 2023 at a certain hospital was collected. Patients were divided into thyroid immune-related adverse event （irAE） group （subdivided into clinical hypothyroidism， clinical hyperthyroidism， subclinical hypothyroidism， and subclinical hyperthyroidism subgroups） and non- thyroid irAE group based on whether they experienced immune-induced thyroid irAE. Univariate and multivariate Logistic regression analyses were employed to analyze the influencing factors of ICI-related thyroid adverse events. RESULTS A total of 382 patients who received ICI treatment were included， with 137 cases in the thyroid irAE group （accounting for 35.9%） and 245 cases in the non-thyroid irAE group （accounting for 64.1%）. Multivariate Logistic regression analysis， following univariate screening， revealed that ICI combined with radiotherapy was positively associated with the occurrence of thyroid irAE [odds ratio （OR）＝2.157， 95% confidence interval （CI） （1.144， 4.066）， P＜0.05]， while lung squamous cell carcinoma was negatively associated with the occurrence of thyroid irAE [OR＝0.600， 95%CI （0.369， 0.975）， P＜0.05]. Among various thyroid irAE， nasopharyngeal malignancy was positively associated with the occurrence of immune-related clinical hyperthyroidism [OR＝4.678， 95%CI （1.149， 19.042）， P＜0.05]； ICI combined with radiotherapy [OR＝2.622， 95%CI （1.227， 5.603）， P＜0.05] and lung adenocarcinoma [OR＝2.013， 95%CI （1.078， 3.759）， P＜0.05] were positively associated with the occurrence of immune-related subclinical hyperthyroidism. Age was negatively associated with the occurrence of immune-related clinical hypothyroidism [OR＝0.944， 95%CI （0.896， 0.995）， P＜0.05]； age [OR＝0.963， 95%CI （0.932， 0.994）， P＜0.05] and ICI combined with chemotherapy [OR＝0.332， 95%CI （0.137， 0.802）， P＜0.05] were negatively associated with the occurrence of immune-related subclinical hypothyroidism. CONCLUSIONS Among patients receiving ICI treatment， younger patients are more prone to thyroid irAE. Patients receiving ICI combined with chemotherapy are less likely to experience subclinical hypothyroidism， while ICI combined with radiotherapy significantly increases the risk of thyroid adverse events.

AIM: To explore the control effects of wearing orthokeratology lens for 1 a on adolescent myopia patients with different diopters.METHODS: Prospective non-randomized controlled study. A total of 120 adolescent myopic patients(224 eyes), with an average age of 11.00±2.08 years old, who were fitted with orthokeratology lenses in the optometry department of our hospital from November 2022 to May 2023 were collected. There were 3 groups according to the spherical equivalent, including 86 eyes in the group of -0.50--2.00 D, 99 eyes in the group -2.25--4.00 D, and 39 eyes in group -4.25--6.00 D. Patients were followed up for 1 a to observe the changes of uncorrected visual acuity, axial length, corneal curvature, corneal central thickness and corneal endothelial cells density in the three groups after wearing lens for 1 a.RESULTS:A total of 113 cases(212 eyes)were followed up for 1 a, including 82 eyes in the group of -0.50--2.00 D, 95 eyes in the group of -2.25--4.00 D, and 35 eyes in the group of -4.25--6.00 D. There was no statistical difference in corneal central thickness and corneal endothelial cell density among the three groups of patients after wearing lens for 1 a(all P>0.05). Uncorrected visual acuity was significantly improved, and flat kerotometry(FK)and steep kerotometry(SK)were significantly flatter(both P<0.01). Furthermore, the growth of axial length in the three groups of patients after wearing lens for 1 a was 0.21±0.26, 0.13±0.21 and 0.09±0.10 mm, respectively(P<0.05). There were differences between the -0.50--2.00 D group and the -2.25--4.00 D group and -4.25--6.00 D group(P=0.028, 0.010), and there were no differences between the -2.25--4.00 D group and the -4.25--6.00 D group(P=0.344).CONCLUSION:It is safe and effective for young myopia patients to wear orthokeratology lenses, which can prevent the non-benign growth of the axial length and effectively delay the development of myopia, and the myopia control effect is better especially for myopia patients of above -2.0 D.

Objective To investigate the effect and mechanism of dabrafenib （DAB） combined with tremelimumab （TREM） on melanoma. Methods The effects of DAB combined with TREM on cell viability, cytotoxicity and cell migration of A375 cells were evaluated by Cell Counting Kit-8 （CCK-8） method, lactate dehydrogenase （LDH） method and scratch assay. The levels of reactive oxygen species （ROS）, adenosine triphosphate （ATP）, malondialdehyde （MDA）, and superoxide dismutase （SOD） were detected to evaluate the effects of combined drugs on oxidative stress and energy metabolism. In addition, A375 tumor-bearing nude mice model was used to evaluate the inhibitory effect of the combined treatment on tumor growth in vivo, and the degree of cell apoptosis and cell proliferation in tumor tissues were analyzed by terminal deoxynucleotidyl transferase-mediated dutP Nick end labeling （TUNEL） and proliferating cell nuclear antigen （PCNA） immunohistochemical staining. Results The combined treatment significantly inhibited the survival rate and migration ability of A375 cells and enhanced the cytotoxicity. The combined intervention also significantly increased ROS level, decreased ATP, SOD and MDA levels. It effectively inhibited tumor growth in tumor-bearing nude mice, increased the apoptosis rate of tumor cells and inhibited cell proliferation. Conclusion DAB combined with TREM may improve the therapeutic effect of melanoma by enhancing oxidative stress, inhibiting energy metabolism, and promoting cell apoptosis. This combination therapy may provide a new therapeutic strategy to overcome the limitations of singledrug therapy.

OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Traditional Chinese medicine (TCM) serves as a treasure trove of ancient knowledge, holding a crucial position in the medical field. However, the exploration of TCM's extensive information has been hindered by challenges related to data standardization, completeness, and accuracy, primarily due to the decentralized distribution of TCM resources. To address these issues, we developed a platform for TCM knowledge discovery (TCMKD, https://cbcb.cdutcm.edu.cn/TCMKD/). Seven types of data, including syndromes, formulas, Chinese patent drugs (CPDs), Chinese medicinal materials (CMMs), ingredients, targets, and diseases, were manually proofread and consolidated within TCMKD. To strengthen the integration of TCM with modern medicine, TCMKD employs analytical methods such as TCM data mining, enrichment analysis, and network localization and separation. These tools help elucidate the molecular-level commonalities between TCM and contemporary scientific insights. In addition to its analytical capabilities, a quick question and answer (Q&A) system is also embedded within TCMKD to query the database efficiently, thereby improving the interactivity of the platform. The platform also provides a TCM text annotation tool, offering a simple and efficient method for TCM text mining. Overall, TCMKD not only has the potential to become a pivotal repository for TCM, delving into the pharmacological foundations of TCM treatments, but its flexible embedded tools and algorithms can also be applied to the study of other traditional medical systems, extending beyond just TCM.

Objective:To prepare the anti-programmed death-ligand 1 (PD-L1) nanoantibody P3C8-C3Fab by ligating with C3Fab and to investigate its role in plasma half-life.Methods:The C3Fab peptide derived from protein G was molecularly fused with the nanobody P3C8 by DNA recombination technology. The nanoantibody P3C8-C3Fab was inducibly expressed and purified in the E. coli BL21 strain, and the binding of it to PD-L1 protein, mouse IgG, and PD-L1-expressing tumor cells was detected by enzyme-linked immunosorbent assay (ELISA). The residual P3C8-C3Fab was detected in mouse serum at different times using double-antibody sandwich ELISA to assess the prolongation of the plasma half-life of PD-L1 nanobodies by C3Fab. Results:The nanoantibody P3C8-C3Fab was successfully constructed, and it could efficiently express itself in soluble form in BL21. The purified NbP3C8-C3Fab protein was obtained with a mass fraction of about 90% at a yield of 7.18 mg/L. The affinity of P3C8-C3Fab for PD-L1 protein and mouse IgG gradually increased with increasing mass concentration and showed a concentration correlation. The binding of P3C8-C3Fab to lung cancer A549 cells showed a concentration correlation. The concentration standard curve of P3C8-C3Fab in mouse serum showed a typical S-shape with a concentration correlation. The plasma half-life of P3C8 was only 0.44 h, while the plasma half-life of P3C8-C3Fab was 21.27-fold higher, up to 9.36 h.Conclusions:The linkage of C3Fab to the nanobodies of P3C8 can significantly prolong the plasma half-life of P3C8, which is valuable for the improvement of in vivo nanobody effects.

ObjectiveTo establish a dose-effect curve for semi-automatic analysis of dicentric chromosomes(DC) based on an automatic chromosome analysis system. Methods A total of three healthy volunteers were recruited as the study subjects, and their peripheral blood was collected and stimulated by X-ray at doses of 0.00, 0.10, 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 4.00, and 5.00 Gy, with the absorbed dose rate of 1.0 Gy/min. Images of DC in the mid-stage of cell division were collected using a high-throughput automatic chromosome analysis system. The DCScore software was used to automatically analyze DC aberrations, and a dose-effect curve for semi-automatic analysis of DC was fitted after manual confirmation. The fitted dose-effect curve for semi-automatic analysis of DC was validated for accuracy using three proficiency test samples from the national quality assessment of biological dose. Results The incidence of DC increased with increasing irradiation doses in the range of 0.00-5.00 Gy (P<0.01). The dose-effect curve for the fitted semi-automatic analysis of DC was ŷ =0.000 8 (±0.000 2) +0.009 2(±0.000 9) D+0.014 2(±0.000 4) D² (R²= 0.999 8). The relative deviation between the estimated dose and the actual dose of the three test samples was about 20.00%, indicating curve applicability for biological dose estimation. Moreover, excluding the time spent on manual analysis, the semi-automatic analysis method increased the analysis efficiency by 26.0 times. Conclusion The semi-automatic analysis dose-effect curve for DC stimulated by X-ray is constructed for biological dose estimation, which can reduce the manual analysis time, and holds great potential for application in nuclear emergency response to large-scale radiation accidents.

Objective:To explore the effect of complement component C1s on the proliferation,migration and adhesion of esophageal squamous cell carcinoma(ESCC)cells and on the growth of xenograft tumors in nude mice.Methods:The C1S mRNA ex-pression of ESCC tissues and adjacent normal tissues(ANTs)were analyzed using NCBI-GEO database.The C1s expression of ESCC cell lines was analyzed with RT-qPCR and Western blot.The knockdown or overexpression of C1s in ESCC cells lines was performed using C1s small interfering RNA(siRNA),C1s short hairpin RNA(shRNA)or C1s overexpression lentivirus,and the cell prolifera-tion was detected by CCK-8 assay,cell migration was detected by cell wound healing assay,cell adhesion was detected by cell-matrix adhesion assay,the expressions of matrix metalloproteinases MMP1 and MMP13 were detected by Western blot,and the effect of C1s on the growth of xenograft tumors in nude mice was detected by subcutaneous tumorigenesis assay in nude mice.The expression of CD34 in the xenograft tumors was detected by immunohistochemistry,and the formation of tumor microvessel was analyzed.Results:The expression of C1S mRNA in ESCC tissues was significantly higher than that in ANTs.Knockdown of C1s significantly suppressed proliferation,migration and cell-matrix adhesion of ESCC cells,as well as growth of xenograft tumors in nude mice,while overexpres-sion of C1s had the opposite effects.The expressions of MMP1 and MMP13 were decreased in ESCC cells TE-1 with C1s knockdown.Compared with control group,the microvessel of the xenograft tumors in the C1s overexpression group were more abundant.Conclu-sion:C1s is significantly upregulated in ESCC tissues,and promotes proliferation,migration,cell-matrix adhesion of ESCC cells,and the growth of xenograft tumors.C1s may play an important role in the occurrence and development of ESCC.

Objective To develop a blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia and test its reliability and validity.Methods The initial questionnaire was formed through literature review,expert consultation,two rounds of Delphi letter consultation,and pre-survey.From August to September 2019,a total of 125 perioperative patients with hyperglycemia who were hospitalized in the surgical ward of the First Affiliated Hospital of Xi'an Jiaotong University were selected as the survey objects by the convenient sampling method.The items of the questionnaire were screened and the reliability and validity were tested.Results A total of 125 questionnaires were distributed and 115 valid questionnaires were returned,with an effective recovery rate of 92.0%.The blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia included five dimensions(17 items in total),including influencing factors and hazards of abnormal blood glucose,key points of preoperative and postoperative nursing observation,perioperative blood glucose control goals,perioperative blood glucose management points,and emergency treatment of perioperative critical conditions.The effective recovery rates for both rounds of inquiry are 100.00%,the expert authority coefficient was 0.880 and the average coefficient of variation was 0.086 and 0.065(P＜0.01).Exploratory factor analysis extracted a total of five common factors,and the cumulative variance contribution rate was 79.895%.The Cronbach's α coefficient of the questionnaire was 0.905,the test-retest reliability was 0.955,and the content validity index was 0.968.Conclusions The blood glucose management knowledge questionnaire for perioperative patients with hyperglycemia is scientific and practical,which can be used as an effective tool to evaluate the blood glucose management knowledge level during perioperative period.

Objectives:To explore the imaging features of patients with isolated left ventricular apical hypoplasia(ILVAH). Methods:Twelve patients diagnosed with ILVAH(ILVAH group)in our hospital from April 2018 to August 2023 were enrolled,and all of them received transthoracic echocardiography(TTE)examination;9 patients underwent CMR examination;and 1 patient underwent CT examination.Clinical data and imaging characteristics of the patients were analyzed.At the same time,twelve healthy age and sex matched participants who underwent physical examination in the same period were selected as the control group. Results:TTE showed that:compared with the control group,the left ventricular transverse diameter([46.3±5.7]mm vs.[57.8±12.6]mm)and right ventricular long diameter([62.0±4.2]mm vs.[73.6±6.4]mm)were larger in the ILVAH group(P＜0.05),the left ventricular long diameter([63.0±3.5]mm vs.[53.4±8.2]mm)was smaller(P＜0.05).There was no significant difference in right ventricular transverse diameter between the two groups(P＞0.05).The interventricular septum was convex to the right ventricle,and the thickness at the apex was(5.2±2.0)mm in the ILVAH group.The papillary muscles were all attached to the flat left ventricular apex.Among the 9 patients who underwent CMR examination,adipose tissue replacement was found in the left ventricular apex in 7 out of the 9 patients,and endocardial fibrosis was found in 2 out of the 9 patients. Conclusions:The clinical presentation of ILVAH is non-specific,but there are specific imaging manifestations that may help improve the understanding of the disease.