OBJECTIVE To investigate the clinical characteristics of euglycemic diabetic ketoacidosis （euDKA） induced by empagliflozin， and provide references for safe medication. METHODS Case reports of euDKA induced by empagliflozin were retrieved and analyzed from PubMed， Web of Science， CNKI， and Wanfang Data. The Naranjo’s scale was adopted to assess the causal relationship between empagliflozin and euDKA. RESULTS A total of 29 patients were enrolled， including 16 males and 13 females，with a median age of 58 years. All patients were diagnosed with type 2 diabetes mellitus； 22 patients had at least one comorbidity. The median time to euDKA onset was 60 days after administration， and 7 cases occurred within 2 weeks of treatment. Perioperative periods，fasting，and low-carbohydrate or ketogenic diets were the main predisposing factors. Common presentations included nausea，vomiting， fatigue， tachypnea，and tachycardia. The causal relationship between empagliflozin and euDKA was assessed as “probable” in all cases. According to adverse reaction severity grading， 13 cases were grade 3 （severe） and 16 cases were grade 4 （life-threatening）. All patients discontinued empagliflozin and recovered after corresponding treatment. CONCLUSIONS euDKA is a serious adverse reaction to empagliflozin， which mostly occurs early in treatment. Perioperative periods， fasting， and ketogenic diets are prone to induce euDKA. Elderly patients and those with comorbidities are at higher risk. Risk assessment should be conducted before clinical administration； blood ketones and acid-base monitoring should be strengthened in the early medication period； withhold the drug before elective surgery， avoid prolonged fasting；upon diagnosis， discontinue empagliflozin and initiate intravenous insulin， provide fluid resuscitation promptly， and use other treatments to improve patient prognosis.

Objective: To explore the core features of trait aggression in children and adolescents, so as to provide a theoretical basis for behavioral interventions targeting the central psychological characteristics of aggression in children and adolescents. Methods: From March to May 2020, a simple random convenience sampling method was employed to recruit 39 165 students from grades 4 to 12 in Sichuan, Chongqing, Guizhou, and Shandong. Data were collected via online questionnaires, with all participants completing the Chinese Version of the Aggression Questionnaire. Psychometric network analysis was utilized for data processing. Results: Trait aggression among Chinese children and adolescents was at a moderately low level. The core nodes of the network structure included physical aggression [if someone intentionally causes trouble for me, I will hit them severely (AGG6); if someone hits me, I will retaliate (AGG11)] and self aggression [When I am very irritable, I think of hurting myself (AGG5); when I am in a bad mood, I engage in behaviors that harm my health, such as overeating (AGG25)]. Across grade levels, core nodes primarily originated from the anger dimension [When I m angry, I feel like a powder magazine that could explode at any moment (AGG13); I can t control my temper (AGG18); I am prone to getting angry when I see things that are not pleasing to the eye (AGG23); I will get angry for no reason (AGG27)]. Except for grades 7 and 9, core nodes in other grades included the verbal aggression dimension [I am prone to arguments with people (AGG22)]. Before grade 8, core nodes incorporated the self aggression dimension (AGG 5, AGG 25); after grade 8, core nodes included the physical aggression dimension [AGG 6, AGG 11, I fight slightly more than others (AGG16), and if people around me make things difficult for me to a certain extent, I will fight with them (AGG26)]. No statistically significant differences were found in the trait aggression network structures across grades, genders, or within gender comparisons of different grades. Conclusion These findings broaden our understanding of aggression in children and adolescents, suggesting that behavioral interventions can effectively reduce aggressive behaviors in this population.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To evaluate the clinical value of high-risk human papillomavirus (HPV) viral load for the cervical cancer screening and triage of high-risk HPV positive populations without additional tests.Methods:(1) This study conducted a retrospective analysis of 29 720 women aged 35-64 years who received cervical cancer screening in Quanzhou, China, in 2021. Fourteen high-risk HPV types (including HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) were detected for cervical cancer primary screening using hybrid capture-chemiluminescence method. High-risk HPV positive samples were further subjected to HPV 16/18 genotyping using hybrid capture-chemiluminescence method. Among them, HPV 16/18 positive women were directly referred to colposcopy, while the other 12 high-risk HPV positive samples were further subjected to liquid based cytology test. Those with abnormal or suspicious cytology were referred to colposcopy. Biopsies were taken for histopathological examination of suspicious or abnormal individuals under colposcopy. (2) Ten cases of colposcopy loss or refusal to undergo examination were excluded, and the data from the 29 710 cases were analyzed. The HPV viral loads of the other 12 high-risk HPV positive populations were focused and evaluated their HPV viral loads for further cervical intraepithelial neoplasia (CIN) Ⅱ and above lesions (CINⅡ +) triage in cervical cancer screening. Results:(1) Among 29 720 women, 2 487 women (8.37%, 2 487/29 720) were positive for high-risk HPV, including 807 women (2.72%, 807/29 720) were positive for HPV 16/18 and 1 680 patients (5.65%, 1 680/29 720) were positive for the other 12 high-risk HPV types. Among 1 680 women who tested positive for the other 12 high-risk HPV types, 573 patients were atypical squamous cell carcinoma of unclear significance or above, 346 patients were CIN Ⅰ, 122 patients were CIN Ⅱ-Ⅲ, 9 patients were squamous cell carcinoma patients, and 4 patients were adenocarcinoma in situ. The immediate risk of CIN Ⅱ + in HPV 16/18 positive women (11.13%) was approximately four times higher than that of other 12 high-risk HPV positive women (2.74%). (2) Through the viral load analysis of the other 12 high-risk HPV types, we found that the viral load of the other 12 high-risk HPV provide a good value for the pathological results, with a clinical cutoff (CO) value of 11.21 relative light unit/CO (RLU/CO) for the CINⅡ + detection. Except for HPV 16/18 positive patients, when the viral load values of the other 12 high-risk HPV types were greater than 10 RLU/CO, these patients had a higher risk of CINⅡ +, with a positive predictive value of 31.29%. CINⅡ + was not found in any of the other 12 high-risk HPV positive with viral load values less than or equal to 10 RLU/CO. Conclusions:Using hybrid capture-chemiluminescence HPV tests for HPV 16/18 genotyping, combined with the viral loads (>10 RLU/CO) of the other 12 high-risk HPV analysis, one could triage HPV positive population without additional tests. Such triage strategy could promote the coverage of cervical cancer screening, particularly where cytology pathologists or economic resources are limited.

Objective:To explore the effects of peripheral nerve injury(PNI)on neuropathic pain(NP)and memo-ry function in mice,as well as the activation of neurons in the paraventricular nucleus(PVT)of the thalamus,so as to provide a basis for studying the relationship between NP and memory impairment.Methods:Twenty one 8-week-old male C57 BL/6J mice were randomly divided into sham group and experimental group,and the routine spared nerve inju-ry(SNI)was constructed in the mice of experimental group.The pain behavior and memory impairment of mice after SNI were evaluated with hot plate and eight-arm maze behavioral tests.Pearson correlation analysis was performed to an-alyze the correlation between pain behavior and memory impairment.The c-FOS expression in PVT was detected with immuno-staining.Results:Compared with the sham group,the heat pain threshold of mice in the experimental group was significantly reduced(P＜0.001).The results of the eight-arm maze test showed that the total rest time was signifi-cantly increased(P＜0.001),and the working memory error was increased from 1 to 4 days after SNI(P＜0.01).Correlation analysis indicated that early working memory errors were negatively correlated with heat pain threshold after SNI(P＜0.001).The immunofluorescence revealed that the number of c-FOS positive cells in PVT increased signifi-cantly(P＜0.001).Conclusion:SNI can cause abnormal pain behavior and memory impairment in mice,and cause neuronal activation in PVT.This study provides a basis for neurons in PVT to participate in the regulation of memory impairment in the context of NP.

Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.

Objective To explore practical pathways for the connotation quality control of Zhuang medical records by le-veraging the reform of DRG-based medical insurance payment systems as an opportunity,thereby enhancing record quality and fostering the coordinated development of ethnic medicine with modern medical insurance payment systems.Methods By analy-zing the requirements imposed by the DRG-based payment reform on the quality management of Zhuang medical records,a quality control management system focused on the connotation quality control of these records was established.A scoring standard for the connotation quality of Zhuang medical records,supplemented by DRG,was developed.Dynamic quality control was implemented through a combination of information-based intelligent review and expert manual review to ensure rectification.Results Key in-dicators,such as the qualification rate of the first page of medical records,the A-level rate of inpatient records,and the DRG en-rollment rate,showed significant improvements.The documentations of surgical and procedural records were standardized,and the records of ward rounds and case discussions by senior physicians were comprehensive and detailed,accurately reflecting the diagnostic and therapeutic methods and outcomes of Zhuang medicine.Conclusion The DRG-based quality control model for Zhuang medical records effectively aligns medical insurance payment with the unique characteristics of ethnic medicine,offering a replicable model for the quality management of medical records in ethnic medicine institutions under DRG-based reforms.

Objective To verify the mechanism of bromodomain PHD finger transcription factor(BPTF)affecting develop-ment of glioma and ferroptosis by regulating the expression of solute carrier family 40 member 1(SLC40A1)in glioma cells by in v itro and invivo experiments.Methods U87MG cells were divided into sh-NC group,sh-BPTF group,sh-BPTF+ov-NC group and sh-BPTF+ov-SLC40A1 group.Cell lines were stably transfected by lentivirus,and the transfection efficiency was verified by qRT-PCR and Western blotting.Cell proliferation ability was detected by CCK-8 and plate clone formation test.Cell migra-tion and invasion ability were detected by Transwell.Cells were injected subcutaneously into nude mice to detect the tumor growth.To evaluate theferroptosis of cells,the reactive oxygen species(ROS)level,iron content,malondialdehyde(MDA)con-tent and reduced glutathione/oxidized glutathione(GSH/GSSG)ratio in cells were detected by corresponding kits.Co-immuno-precipitation(Co-IP)experiment was used to verify the interaction between BPTF and c-Myc protein.Chromatin immunoprecipi-tation(ChIP)experiment was used to verify that BPTF and c-Myc combined with SLC40A1 promoter.Double luciferase reporter gene experiment was used to verify theeffect of BPTF on SLC40A1 transcription.Results After BPTF knockdown,theexpres-sion of SLC40A1 in glioma cell was decreased,cell proliferation,migration,invasion in vitro,and tumor growth in vivo were in-hibited,iron content,ROS level and MDA content in cells were increased,and GSH/GSSG ratio in cell was de-creased.Overexpression of SLC40A1 reversed the inhibitory effect of BPTF on the proliferation,migration,invasion and tumor grow th in vivo,decreased the iron content,ROS level and MDA content in cells,and increased the GSH/GSSG ratio in cells.There was an interaction between BPTF and c-Myc proteins in gliomacells.A potential binding site of c-Mycin SLC40A1 promoter was verified,BPTF and c-Myc protein bound to SLC40A1 promoter.BPTF knockdown reduced the transcriptional ac-tivity of SLC40A1 promoter,and BPTF knockdown after binding site mutation did not affect the transcriptional activity of SLC40A1 promoter.Conclusion BPTF may upregulate the expression of its downstream target gene SLC40A1 by interacting with c-Myc,thereby inhibiting ferroptosis in glioma cells and promoting glioma progression.

OBJECTIVE: To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group. METHODS: A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject. A retrospective study was conducted to collect the proband's clinical data. The proband's erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods. Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents. Genomic DNA was extracted from the proband's blood sample for whole genome sequencing (WGS) and erythrocyte blood group gene analysis, with validation by Sanger sequencing. Multiple bioinformatics tools were used to analyze the pathogenicity of the variant. The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing. This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201). RESULTS: The proband was a 91-year-old Han Chinese male with prostatitis, cystitis, and malnutrition in conjunct with emaciation. He had a history of multiple erythrocyte transfusions without observable adverse reactions. Prior to the most recent transfusion, major crossmatch agglutination was observed, which prompted antibody identification. Antibodies against high-frequency antigens were detected in the proband's serum, with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems, e.g., MNS, LU, KEL. WGS analysis identified 4 525 SNPs and 1 046 INDEL variants among erythrocyte blood group genes. Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant. This variant in the ABCB6 gene (c.459delC) has led to a frameshifting mutation (p.Trp154GlyfsTer96), resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum. CONCLUSION This study has identified anti-Lan alloantibodies in a Lan-negative patient and, for the first time, elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.
Humans ; Male ; Blood Group Antigens/immunology* ; Aged, 80 and over ; Retrospective Studies ; ATP-Binding Cassette Transporters

Objective:To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group.Methods:A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject. A retrospective study was conducted to collect the proband′s clinical data. The proband′s erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods. Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents. Genomic DNA was extracted from the proband′s blood sample for whole genome sequencing (WGS) and erythrocyte blood group gene analysis, with validation by Sanger sequencing. Multiple bioinformatics tools were used to analyze the pathogenicity of the variant. The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing. This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201).Results:The proband was a 91-year-old Han Chinese male with prostatitis, cystitis, and malnutrition in conjunct with emaciation. He had a history of multiple erythrocyte transfusions without observable adverse reactions. Prior to the most recent transfusion, major crossmatch agglutination was observed, which prompted antibody identification. Antibodies against high-frequency antigens were detected in the proband′s serum, with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems, e. g., MNS, LU, KEL. WGS analysis identified 4 525 SNPs and 1 046 INDEL variants among erythrocyte blood group genes. Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant. This variant in the ABCB6 gene (c.459delC) has led to a frameshifting mutation (p.Trp154GlyfsTer96), resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum. Conclusion:This study has identified anti-Lan alloantibodies in a Lan-negative patient and, for the first time, elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.