Objective: To analyze the serological phenotypes and molecular genetic characteristics of a proband with ABO forward and reverse typing discrepancy and their family members, and to investigate the molecular genetic mechanism underlying the Ael/AelB phenotype caused by the c. 575T>C variant on an ABO A1.02 background. Methods: Serological testing and adsorption-elution assays were performed for blood group identification of the proband and family members. PCR-SBT, cloning sequencing, and Nanopore third-generation sequencing were used to analyze ABO gene variants and haplotypes. Phyre2 and PyMOL were used to predict the effect of the p. Ile192Thr variant on the structure of glycosyltransferase A (GTA), and plasma GTA activity was evaluated using an in vitro transferase assay. Results: Among thirteen family members, four members showed a serological phenotype consistent with the Ael subtype and one with the AelB subtype. Cloning sequencing and third-generation sequencing confirmed that five family members carried the ABO A1.02 (c. 575T>C) variant, which co-segregated with the weak A phenotype in the family. Structural modeling suggested that p. Ile192Thr may alter the local spatial conformation and hydrogen-bond interactions of GTA. Plasma GTA activity testing showed markedly reduced GTA activity in the tested individuals. Conclusion: The ABO A1.02 (c. 575T>C) variant is associated with the Ael/AelB phenotype. The p. Ile192Thr substitution may weaken A antigen expression by altering GTA conformation and reducing enzymatic activity. This study provides additional evidence for the role of this variant in the Ael/AelB phenotype from the perspectives of familial inheritance, full-length haplotype analysis, and functional assessment, which is important for accurate ABO subtype identification and individualized transfusion strategies.

OBJECTIVE: To investigate the effects of thymoquinone on the proliferation of acute myeloid leukemia (AML) cells and its molecular mechanism, so as to provide theoretical basis for the basic research on the anti-leukemia of traditional Chinese medicine. METHODS: The HL-60 and THP-1 cells were treated with thymoquinone at different concentration gradients, cell proliferation was detected by CCK-8 method, morphological changes were detected by Wright-Giemsa method, apoptosis was detected by Annexin V/PI double staining flow cytometry, and apoptosis and signal pathway protein expression were detected by Western blot. Real-time quantitative fluorescence PCR and Western blot were used to detect the expression changes of high mobility family members of SRY-related proteins (SOX). RESULTS: Thymoquinone inhibited the malignant proliferation of HL-60 and THP-1 cells, up-regulated the expression of pro-apoptotic protein Bax, down-regulated the expression of anti-apoptotic protein Bcl-2 and Survivin, and hydrolyzed Caspase-3 to induce the apoptosis of HL-60 and THP-1 cells. Thymoquinone could also significantly down-regulate the phosphorylation of PI3K, Akt and mTOR, and inhibit the malignant biological characteristics of HL-60 and THP-1 cells by inhibiting the activation of PI3K/Akt/mTOR pathway. After thymoquinone intervention in HL-60 and THP-1 cells, the expression of SOX2 and SOX4 could be down-regulated significantly. At low concentration ( < 10 μmol/L), the expression of SOX12 was weakly affected by thymoquinone. With increasing concentration, the expression of SOX12 could be down-regulated, however, thymoquinone had no effect on SOX11 expression. CONCLUSION Thymoquinone can inhibit the proliferation of AML cells, and its mechanism may be related to inhibiting the activation of PI3K/Akt/mTOR signaling pathway, regulating the expression of apoptotic proteins and core members of SOX family.
Humans ; Benzoquinones/pharmacology* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/metabolism* ; Apoptosis/drug effects* ; HL-60 Cells ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/metabolism* ; THP-1 Cells

Objective:To investigate the clinical application effects of the pedicled anterior intercostal artery perforator flap in breast reconstruction after breast-conserving surgery for breast cancer.Methods:This study was a retrospective observational study. From January to December 2023, 16 female breast cancer patients who met the inclusion criteria were hospitalized in the Department of Breast Surgery of the Affiliated Hospital of Southwest Medical University, with the age of (48±8) years. The pedicled anterior intercostal artery perforator flap was used for breast reconstruction of patients after breast-conserving surgery. After complete resection of tumor tissue, a "crescent-shaped" incision was designed at the inframammary fold. The pedicled anterior intercostal artery perforator flap was harvested based on the tumor location and the defect area after tumor removal. The flap was de-epithelialized, coapted, and rotated anterogradely or retrogradely to fill the defect. The donor site wound was closed with layered sutures. The following parameters were recorded: breast tissue loss volume during surgery, surgical duration, retention duration of the drainage tube, positive proportion of tumors in the breast incision margin tissue, breast loss ratio, flap survival, and incidence ratio of complications after operation. Patients were followed up for local recurrence or distant metastasis of tumor. At the last follow-up, the Ueda score was used to evaluate cosmetic outcomes of reconstructed breasts after breast-conserving surgery, and the Breast-Q scale version 2.0 was applied to assess patients' satisfaction and quality of life with breast reconstruction after breast-conserving surgery.Results:The breast tissue loss volume during surgery in this group of patients was 20-128 (59±34) cm3, the surgical duration was 105-200 (143±27) min, the retention duration of the drainage tube was 3-7 (4.6±1.0) d, and the positive proportion of tumors in the breast incision margin tissue was 1/16, with breast loss ratio of 0. After the surgery, the patient's transplanted flaps all survived. One patient had postoperative fat liquefaction in the surgical area, and the incidence ratio of postoperative complications was 1/16. The patients were followed up for 3-12 (11±4) months, and no local breast cancer recurrence or distant metastasis occurred. At the last follow-up, the cosmetic score of breast reconstruction after breast-conserving surgery were excellent in 6 cases, good in 8 cases, and fair in 2 cases, with an excellent and good ratio of 14/16. At the last follow-up, the highest score in the evaluation of patients' satisfaction with breast reconstruction and quality of life after breast-conserving surgery was the satisfaction with the surgeons, with a score of 59-100 (91±13), followed respectively by physiological health of the chest with a score of 60-100 (77±14), psychological health with a score of 35-100 (74±20), breast satisfaction with a score of 55-100 (73±13), satisfaction with information acquisition with a score of 53-100 (70±14), and sexual health with a score of 34-100 (70±23).Conclusions:The pedicled anterior intercostal artery perforator flap is safe and reliable for breast reconstruction after breast-conserving surgery for breast cancer, and can achieve high cosmetic effects and patient satisfaction. This flap is simple in design, easy to operate and highly reproducible, and is worthy of clinical promotion and application.

Background and Aims:Oncoplastic breast-conserving surgery(OBCS)integrates oncologic and plastic surgical techniques and includes two primary approaches:volume displacement and volume replacement.The pedicled lateral thoracic artery perforator(LTAP)flap is a commonly used technique for volume replacement.Although recent studies in China have confirmed its safety in OBCS,its patient-reported outcomes have not been systematically evaluated,and comparative data with volume displacement techniques remain lacking.Therefore,this study was performed to compare the clinical outcomes and patient satisfaction of LTAP flap versus mammoplasty(volume displacement)in OBCS,to inform surgical decision-making.Methods:A retrospective case-control study was conducted,including 106 patients with unilateral stage 0-Ⅲ breast cancer who underwent OBCS at the Affiliated Hospital of Southwest Medical University from January 2023 to June 2024.Patients were divided into the LTAP flap group(27 cases)and the mammoplasty group(79 cases)based on the surgical technique.Intraoperative variables,cosmetic outcomes,postoperative complications,and Breast-Q scores before and after surgery were compared between the two groups.Results:There were no significant differences between the two groups in clinicopathological characteristics or preoperative Breast-Q scores(all P>0.05).The LTAP group had longer operative times,larger excised tissue volumes,and greater postoperative drainage volumes(all P<0.001).Postoperative cosmetic outcomes were significantly better in the LTAP group,with a higher rate of excellent-to-good cosmetic results(88.9%vs.57.3%)and higher Breast-Q scores in breast satisfaction,psychosocial well-being,and physical well-being(all P<0.05).There were no significant differences in complication rates or local recurrence between the two groups(all P>0.05).Conclusion:In OBCS,the LTAP flap demonstrates comparable safety to mammoplasty while achieving superior cosmetic outcomes and patient satisfaction.It is particularly suitable for patients with small breast volumes requiring large tissue excision and holds promise for broader clinical application.

OBJECTIVE: To explore the application value and clinical effect of 3D printing combined with customized bone plate in the treatment of acetabular fracture. METHODS: From June 2020 to June 2022, 11 patients with acetabular fractures underwent preoperative planning using 3D printing technology and were treated with customized bone plates including 8 males and 3 females, aged 25 to 66 years old. The fractures were classified according to Letournel-Judet:4 posterior wall fractures, 2 T-type fractures, 2 transverse posterior wall fractures, 2 double column fractures, and 1 anterior column with posterior semi-transverse fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, postoperative drainage volume, postoperative fracture healing time, and hip function score were recorded and analyzed. RESULTS: The operation time of 11 patients was 80 to 150 min, intraoperative blood volume was 150 to 700 ml, fluoroscopy frequency was 2 to 6, postoperative drainage flow was 60 to 195 ml, and the fracture healing time was 2.5 to 6.0 months. Fracture reduction was evaluated according to Matta score:anatomical reduction in 3 cases and satisfactory reduction in 8 cases. Eleven patients were followed up for 7 to 18 months. The hip Merle d'Aubigne function scores were excellent in 6 cases, good in 3 cases, fair in 1 case and poor in 1 case. Incision fat liquefaction occurred in 1 case and obturator nerve traction in 1 case. CONCLUSION The application of 3D printing technology combined with customized bone plates in the treatment of acetabular fracture is effective. In addition, the printed model can provide the operator with the results of the three-dimensional shape of the fracture, which is convenient for surgical reduction and effectively improves the efficiency of surgery.
Humans ; Female ; Male ; Middle Aged ; Acetabulum/surgery* ; Printing, Three-Dimensional ; Adult ; Aged ; Bone Plates ; Fractures, Bone/surgery* ; Fracture Fixation, Internal/methods*

Objective:To explore the effects of hydroxychloroquine(HCQ)on immune mediators dysregulation in severe infection after chemotherapy in acute myeloid leukemia(AML)and its molecular mechanism.Methods:Bone marrow or peripheral blood samples of 36 AML patients with severe infection(AML-SI)and 29 AML patients without infection(AML-NI)after chemotherapy were collected from the First Affiliated Hospital of Gannan Medical University from August 2022 to June 2023.In addition,the peripheral blood of 21 healthy subjects from the same period in our hospital was selected as the control group.The mRNA expressions of CXCL12,CXCR4 and CXCR7 were detected by RT-qPCR technology,and the levels of IL-6,IL-8 and TNF-α were detected by ELISA.Leukemia-derived THP-1 cells were selected and constructed as AML disease model.At the same time,bone marrow mesenchymal stem cells(BM-MSCs)from AML-SI patients were co-cultured with THP-1 cells and divided into Mono group and Co-culture group.THP-1 cells were treated with different concentration gradients of HCQ.The cell proliferation activity was subsequently detected by CCK-8 method and apoptosis was detected by Annexin V/PI double staining flow cytometry.ELISA was used to detect the changes of IL-6,IL-8 and TNF-α levels in the supernatant of the cell co-culture system,RT-qPCR was used to detect the mRNA expression changes of the core members of the CXCL12-CXCR4/7 regulatory axis,and Western blot was used to detect the expressions of apoptosis regulatory molecules and related signaling pathway proteins.Results:CXCL12,CXCR4,CXCR7,as well as IL-6,IL-8,and TNF-α were all abnormally increased in AML patients,and the increases were more significant in AML-SI patients(P＜0.01).Furthermore,there were statistically significant differences between AML-NI patients and AML-SI patients(all P＜0.05).HCQ could inhibit the proliferation and induce the apoptosis of THP-1 cells,but the low concentration of HCQ had no significant effect on the killing of THP-1 cells.When THP-1 cells were co-cultured with BM-MSCs of AML patients,the levels of IL-6,IL-8 and TNF-α in the supernatance of Co-culture group were significantly higher than those of Mono group(all P＜0.01).After HCQ intervention,the levels of IL-6,IL-8 and TNF-α in cell culture supernatant of Mono group were significantly decreased compared with those before intervention(all P＜0.01).Similarly,those of Co-culture group were also significantly decreased(all P＜0.001).However,the expression of the core members of the CXCL12-CXCR4/7 regulatory axis was weakly affected by HCQ.HCQ could up-regulate the expression of pro-apoptotic protein Bax,down-regulate the expression of anti-apoptotic protein Bcl-2,as well as simultaneously promote the hydrolytic activation of Caspase-3 when inhibiting the activation level of TLR4/NF-κ B pathway,then induce the programmed death of THP-1 cells after intervention.Conclusion:The core members of CXCL12-CXCR4/7 axis and related cytokines may be important mediators of severe infectious immune disorders in AML patients.HCQ can inhibit cytokine levels to reverse immune mediators dysregulation and suppress malignant biological characteristics of leukemia cells.The mechanisms may be related to regulating the expression of Bcl-2 family proteins,hydrolytically activating Caspase-3 and inhibiting the activation of TLR4/NF-κ B signaling pathway.

Background and Aims:Oncoplastic breast-conserving surgery(OBCS)integrates oncologic and plastic surgical techniques and includes two primary approaches:volume displacement and volume replacement.The pedicled lateral thoracic artery perforator(LTAP)flap is a commonly used technique for volume replacement.Although recent studies in China have confirmed its safety in OBCS,its patient-reported outcomes have not been systematically evaluated,and comparative data with volume displacement techniques remain lacking.Therefore,this study was performed to compare the clinical outcomes and patient satisfaction of LTAP flap versus mammoplasty(volume displacement)in OBCS,to inform surgical decision-making.Methods:A retrospective case-control study was conducted,including 106 patients with unilateral stage 0-Ⅲ breast cancer who underwent OBCS at the Affiliated Hospital of Southwest Medical University from January 2023 to June 2024.Patients were divided into the LTAP flap group(27 cases)and the mammoplasty group(79 cases)based on the surgical technique.Intraoperative variables,cosmetic outcomes,postoperative complications,and Breast-Q scores before and after surgery were compared between the two groups.Results:There were no significant differences between the two groups in clinicopathological characteristics or preoperative Breast-Q scores(all P>0.05).The LTAP group had longer operative times,larger excised tissue volumes,and greater postoperative drainage volumes(all P<0.001).Postoperative cosmetic outcomes were significantly better in the LTAP group,with a higher rate of excellent-to-good cosmetic results(88.9%vs.57.3%)and higher Breast-Q scores in breast satisfaction,psychosocial well-being,and physical well-being(all P<0.05).There were no significant differences in complication rates or local recurrence between the two groups(all P>0.05).Conclusion:In OBCS,the LTAP flap demonstrates comparable safety to mammoplasty while achieving superior cosmetic outcomes and patient satisfaction.It is particularly suitable for patients with small breast volumes requiring large tissue excision and holds promise for broader clinical application.

Objective:To investigate the clinical application effects of the pedicled anterior intercostal artery perforator flap in breast reconstruction after breast-conserving surgery for breast cancer.Methods:This study was a retrospective observational study. From January to December 2023, 16 female breast cancer patients who met the inclusion criteria were hospitalized in the Department of Breast Surgery of the Affiliated Hospital of Southwest Medical University, with the age of (48±8) years. The pedicled anterior intercostal artery perforator flap was used for breast reconstruction of patients after breast-conserving surgery. After complete resection of tumor tissue, a "crescent-shaped" incision was designed at the inframammary fold. The pedicled anterior intercostal artery perforator flap was harvested based on the tumor location and the defect area after tumor removal. The flap was de-epithelialized, coapted, and rotated anterogradely or retrogradely to fill the defect. The donor site wound was closed with layered sutures. The following parameters were recorded: breast tissue loss volume during surgery, surgical duration, retention duration of the drainage tube, positive proportion of tumors in the breast incision margin tissue, breast loss ratio, flap survival, and incidence ratio of complications after operation. Patients were followed up for local recurrence or distant metastasis of tumor. At the last follow-up, the Ueda score was used to evaluate cosmetic outcomes of reconstructed breasts after breast-conserving surgery, and the Breast-Q scale version 2.0 was applied to assess patients' satisfaction and quality of life with breast reconstruction after breast-conserving surgery.Results:The breast tissue loss volume during surgery in this group of patients was 20-128 (59±34) cm3, the surgical duration was 105-200 (143±27) min, the retention duration of the drainage tube was 3-7 (4.6±1.0) d, and the positive proportion of tumors in the breast incision margin tissue was 1/16, with breast loss ratio of 0. After the surgery, the patient's transplanted flaps all survived. One patient had postoperative fat liquefaction in the surgical area, and the incidence ratio of postoperative complications was 1/16. The patients were followed up for 3-12 (11±4) months, and no local breast cancer recurrence or distant metastasis occurred. At the last follow-up, the cosmetic score of breast reconstruction after breast-conserving surgery were excellent in 6 cases, good in 8 cases, and fair in 2 cases, with an excellent and good ratio of 14/16. At the last follow-up, the highest score in the evaluation of patients' satisfaction with breast reconstruction and quality of life after breast-conserving surgery was the satisfaction with the surgeons, with a score of 59-100 (91±13), followed respectively by physiological health of the chest with a score of 60-100 (77±14), psychological health with a score of 35-100 (74±20), breast satisfaction with a score of 55-100 (73±13), satisfaction with information acquisition with a score of 53-100 (70±14), and sexual health with a score of 34-100 (70±23).Conclusions:The pedicled anterior intercostal artery perforator flap is safe and reliable for breast reconstruction after breast-conserving surgery for breast cancer, and can achieve high cosmetic effects and patient satisfaction. This flap is simple in design, easy to operate and highly reproducible, and is worthy of clinical promotion and application.

Objective:To investigate the efficacy and side effects of concurrent chemoradiotherapy with or without nimotuzumab in the treatment of locally advanced nasopharyngeal carcinoma after neoadjuvant chemotherapy.Methods:In the prospective study, 100 patients with stage Ⅲ-Ⅳa locally advanced nasopharyngeal carcinoma (except T 3N 0M 0 stage) who met the inclusion criteria were randomly divided into the experimental and control groups using the random number table method. Patients in both groups were treated with neoadjuvant chemotherapy using TPF (paclitaxel liposome, cisplatin, and 5-fluorouracil) regimen for 2 cycles. At 2 weeks after chemotherapy, concurrent chemoradiotherapy plus nimotuzumab targeted therapy was given in the experimental group, and concurrent chemoradiotherapy was delivered in the control group. The main observation index was the distant metastasis-free survival (DMFS) rate. Log-rank test and multivariate Cox regression analysis were used. Results:The objective remission rate and complete remission rate in the experimental and control groups were 100% vs. 98% ( P=1.000) and 92.0% vs. 80% ( P=0.084). The 3-year DMFS in the experimental and control groups were 91.4 % vs. 76.1 % ( P=0.043). The 3-year progression-free survival (PFS), locoregional recurrence-free survival (LRFS) and overall survival (OS) in two groups were 87.3 % vs. 74.1 % ( P=0.097), 94.5 % vs. 85.6 % ( P=0.227) and 90.5% vs. 85.2% ( P=0.444). Subgroup analysis showed that patients with age<60 years ( HR=0.34, 95% CI=0.12-0.94, P=0.037), neutrophil-to-lymphocyte ratio (NLR)≤4 ( HR=0.34, 95% CI=0.13-0.89, P=0.028) received concurrent chemoradiotherapy plus nimotuzumab obtained better PFS. Multivariate analysis showed that NLR was an independent risk factor for disease progression ( HR=5.94, 95% CI=1.18-29.81, P=0.030) and distant metastasis ( HR=13.76, 95% CI=1.52-124.36, P=0.020). Conclusions:Compared with concurrent chemoradiotherapy alone, concurrent chemoradiotherapy combined with nimotuzumab after neoadjuvant chemotherapy can significantly increase DMFS rate for patients with locally advanced nasopharyngeal carcinoma. The incidence of side effects is similar in two groups. Concurrent chemoradiotherapy plus nimotuzumab after neoadjuvant chemotherapy may be a preferred treatment strategy for locally advanced nasopharyngeal carcinoma.

Objective:To construct a nomogram prediction model for predicting the risk of death in patients with sepsis-associated thrombocytopenia (SAT) in intensive care unit (ICU) for early indentification and active intervention.Methods:Clinical data of SAT patients admitted to ICU of the First Affiliated Hospital of Nanjing Medical University from December 2019 to August 2021 were retrospectively collected, including demographic data, laboratory indicators, etc. According to the prognosis at 28 days, the patients were divided into the death group and the survival group, and the differences of clinical variables between the two groups were compared. Multivariate Logistic regression analysis was performed to analyze the independent risk factors influencing mortality of patients within 28 days, then a nomogram predictive model was constructed and its performance was verified with internal data. Receiver operator characteristic curve (ROC curve) was used to evaluate the diagnostic effectiveness of the nomogram model, and the clinical applicability of this model was evaluated by clinical decision curve analysis (DCA).Results:A total of 275 patients were included, with 95 deaths at 28 days and a 28-day mortality of 34.5%. Compared with the survival group, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), sequential organ failure assessment (SOFA), lactic acid (Lac), platelet distribution width (PDW) on day 5 of ICU admission, blood urea nitrogen (BUN), total bilirubin (TBIL), aspartate aminotransferase (AST), C-reactive protein (CRP) of patients in the death group were higher, activated partial thromboplastin time (APTT) and prothrombin time (PT) were longer, platelet count (PLT) on day 3 and day 5 of ICU admission, direct bilirubin (DBIL), fibrinogen (FIB) were lower, the history of chronic lung disease, mixed site infection, lung infection, bloodstream infection, Gram-negative bacterial infection and fungal infection accounted for a higher proportion, the history of diabetes mellitus, urinary tract infection and no pathogenic microorganisms cultured accounted for a lower proportion, and the proportion of the use of vasoactive drugs, mechanical ventilation (MV), continuous renal replacement therapy (CRRT), bleeding events and platelet transfusion were higher. Multivariate Logistic regression analysis showed that APACHEⅡ score at the day of ICU admission [odds ratio ( OR) = 1.417, 95% confidence interval (95% CI) was 1.153-1.743, P = 0.001], chronic lung disease ( OR = 72.271, 95% CI was 4.475-1?167.126, P = 0.003), PLT on day 5 of ICU admission ( OR = 0.954, 95% CI was 0.922-0.987, P = 0.007), vasoactive drug ( OR = 622.943, 95% CI was 10.060-38?575.340, P = 0.002), MV ( OR = 91.818, 95% CI was 3.973-2?121.966, P = 0.005) were independent risk factors of mortality in SAT patients. The above independent risk factors were used to build a nomogram prediction model, and the area under the curve (AUC), sensitivity and specificity were 0.979, 94.7% and 91.7%, respectively, suggesting that the model had good discrimination. The Hosmer-Lemeshow goodness of fit test showed a good calibration with P > 0.05. At the same time, DCA showed that the nomogram model had good clinical applicability. Conclusions:Patients with SAT has a higher risk of death. The nomogram model based on APACHEⅡ score at the day of ICU admission, chronic lung disease, PLT on day 5 of ICU admission, the use of vasoactive drug and MV has good clinical significance for the prediction of 28-day mortality, and the discrimination and calibration are good, however, further verification is needed.