Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

Objective:To investigate impacts of soy isoflavones(SIF)on alveolar bone resorption and inflammatory response in periodontitis rats based on Slit homologue 2(Slit2)/P38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods:Rats were separated into Control group,Model group,SIF low-dose group(L-SIF,25 mg/kg)and SIF high-dose group(H-SIF,75 mg/kg),with 10 rats per group,and periodontitis model was established by ligating necks of maxillary first molars of rats with silk thread except for control group.Rats in L-SIF group and H-SIF group were given corresponding doses of SIF by gavage,Control group and Model group were given same amount of normal saline by gavage,once a day,for 4 consecutive weeks.After administration,serum Slit2,TNF-α,IL-6 and IL-1β levels were detected by ELISA;Micro-CT scan was performed to detect distance between cemen-tumenamel junction and alveolar ridge crest(CEJ-ABC),bone mineral density(BMD),bone volume fraction(BV/TV),and alveolar bone loss was evaluated;HE staining and tartrate-resistant acid phosphatase(TRAP)staining were performed to evaluate tissue inflam-mation,bone resorption and osteoclast activity;expressions of osteoprotegerin(OPG)and receptor activator of nuclear factor κB ligand(RANKL)in periodontal tissues were detected by immunohistochemistry(IHC);Western blot was performed to detect protein expressions of Slit2,P38 MAPK and p-P38 MAPK in periodontal tissues.Results:Compared with Control group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,protein level of Slit2 and p-P38 MAPK/P38 MAPK were greatly increased in Model group,BMD,BV/TV and positive ex-pression of periodontal tissues OPG were greatly decreased(all P<0.05);compared with Model group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,pro-tein levels of Slit2 and p-P38 MAPK/P38 MAPK were greatly decreased,BMD,BV/TV and OPG positive expression of periodontal tissues were greatly increased in L-SIF group and H-SIF group(P<0.05),the above indicators in H-SIF group changed greatly better than L-SIF group(P<0.05).Conclusion:SIF can inhibit alveolar bone resorption and inflammatory response in periodontitis rats and improve periodontitis,whose mechanism may be related to inhibition of Slit2/P38 MAPK signaling pathway.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the influence of curative-intent resection with textbook outcomes of liver surgery (TOLS) on long-term prognosis of gallbladder carcinoma (GBC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 824 patients with GBC in the national multicenter database of Biliary Surgery Group of Elite Group of Chinese Journal of Digestive Surgery, who were admitted to 15 medical centers from January 2014 to January 2021, were collected. There were 285 males and 539 females, aged (62±11)years. According to the evalua-tion criteria of TOLS, patients were divided into those who achieved TOLS and those who did not achieve TOLS. Measurement data with normal distribution were represented as Mean± SD, and com-parison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data were conduc-ted using the Mann-Whitney U test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and the Log-rank test was used for survival analysis. The COX stepwise regression model with backward Wald method was used for univariate and multivariate analyses. Results:(1) Achievement of TOLS. Of the 824 patients undergoing curative-intent resection for GBC, there were 510 cases achieving TOLS and 314 cases not achieving TOLS. (2) Follow-up. Of the 824 patients undergoing curative-intent resection for GBC, after excluding 112 deaths within 90 days after discharge, 712 cases were included for the survival analysis. The median follow-up time, median overall survival time and 5-year overall survival rate of the 510 patients achieving TOLS were 22.1(11.4,30.1)months, 47.6(30.6,64.6)months and 47.5%. The median follow-up time, median overall survival time and 5-year overall survival rate of the 202 patients not achieving TOLS were 14.0(6.8,25.5)months, 24.3(20.0,28.6)months and 21.0%. There was a significant difference in overall survival between patients achieving TOLS and patients not achieving TOLS ( χ2=58.491, P<0.05). (3) Analysis of factors influencing prognosis of patients. Results of multivariate analysis showed that TOLS, carcinoembryonic antigen (CEA), CA19-9, poorly differentiation of tumor, T2 stage of eighth edition of American Joint Committee on Cancer (AJCC) staging, T3 and T4 stage of eighth edition of AJCC staging, N1 stage of the eighth edition of AJCC staging, N2 stage of the eighth edition of AJCC staging, adjuvant therapy were independent factors influencing overall survival time of patients undergoing curative-intent resection for GBC ( hazard ratio=0.452, 1.479, 1.373, 1.612, 1.455, 1.481, 1.835, 1.978, 0.538, 95% c onfidence interval as 0.352-0.581, 1.141-1.964, 1.052-1.791, 1.259-2.063, 1.102-1.920, 1.022-2.147, 1.380-2.441, 1.342-2.915, 0.382-0.758, P<0.05). Conclusion:Patients under-going curative-intent resection for GBC with TOLS can achieve better long-term prognosis.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective:To investigate the clinical efficacy of distal pancreatectomy with celiac axis resection(DP-CAR).Methods:A total of 89 consecutive patients (50 males and 39 females) who were diagnosed with pancreatic body cancer and underwent DP-CAR in Pancreas Center,First Affiliated Hospital of Nanjing Medical University between September 2013 and June 2022 were retrospectively reviewed. There were 50 males and 39 females,with age( M(IQR)) of 63(12) years(range:43 to 81 years). Perioperative parameters,pathology results and follow-up data of these patients were analyzed, χ2 or Fisher′s test for categorical data while the Wilcoxon test for quantitative data. Survival results were estimated by the Kaplan-Meier survival method. Results:Among 89 cases,cases combined with portal vein-superior mesenteric vein or organ resection accounted for 22.5% (20/89) and 42.7% (38/89),respectively. The operative time,blood loss and postoperative hospital stay were 270 (110) minutes,300 (300) ml and 13 (10) days,respectively. The overall morbidity rate was 67.4% (60/89) while the major morbidity was 11.2% (10/89). The increase rate in transient liver enzymes was 42.7% (38/89),3.4% (3/89) for liver failure,53.9% (48/89) for clinically relevant postoperative pancreatic fistula,1.1% (1/89) for bile leak,3.4% (3/89) for chylous leak of grade B and C,11.2% (10/89) for abdominal infection,9.0% (8/89) for postoperative hemorrhage of grade B and C,4.5% (4/89) for delayed gastric emptying,6.7% (6/89) for deep vein thrombosis,3.4% (3/89) for reoperation,4.5% (4/89)for hospital mortality,7.9% (7/89) for 90-day mortality. The pathological type was pancreatic cancer for all 89 cases and pancreatic ductal adenocarcinoma made up 92.1% (82/89). The tumor size was 4.8(2.0) cm, ranging from 1.5 to 12.0 cm. The number of lymph nodes harvested was 14 (13)(range:2 to 33),with a positive lymph node rate of 13.0% (24.0%). The resection R0 rate was 30.0% (24/80) and the R1 (<1 mm) rate was 58.8% (47/80). The median overall survival time was 21.3 months (95% CI: 15.6 to 24.3) and the median disease-free survival time was 19.1 months (95% CI: 11.7 to 25.1). The overall survival at 1-year and 2-year were 69.60% and 39.52%. The median survival time of 58 patients with adjuvant chemotherapy was 24.3 months (95% CI: 17.8 to 32.3) while that of 13 patients without any kind of adjuvant therapy was 8.4 months (95% CI: 7.3 to 22.3). Seven patients accepted neoadjuvant chemotherapy and there was no significant morbidity among them,with a resection rate of R0 of 5/7. Conclusion:DP-CAR is safe and feasible for selective cases,which could be more valuable in improving long-term survival when combined with (neo) adjuvant therapy.

Objective:To investigate the clinical efficacy of distal pancreatectomy with celiac axis resection(DP-CAR).Methods:A total of 89 consecutive patients (50 males and 39 females) who were diagnosed with pancreatic body cancer and underwent DP-CAR in Pancreas Center,First Affiliated Hospital of Nanjing Medical University between September 2013 and June 2022 were retrospectively reviewed. There were 50 males and 39 females,with age( M(IQR)) of 63(12) years(range:43 to 81 years). Perioperative parameters,pathology results and follow-up data of these patients were analyzed, χ2 or Fisher′s test for categorical data while the Wilcoxon test for quantitative data. Survival results were estimated by the Kaplan-Meier survival method. Results:Among 89 cases,cases combined with portal vein-superior mesenteric vein or organ resection accounted for 22.5% (20/89) and 42.7% (38/89),respectively. The operative time,blood loss and postoperative hospital stay were 270 (110) minutes,300 (300) ml and 13 (10) days,respectively. The overall morbidity rate was 67.4% (60/89) while the major morbidity was 11.2% (10/89). The increase rate in transient liver enzymes was 42.7% (38/89),3.4% (3/89) for liver failure,53.9% (48/89) for clinically relevant postoperative pancreatic fistula,1.1% (1/89) for bile leak,3.4% (3/89) for chylous leak of grade B and C,11.2% (10/89) for abdominal infection,9.0% (8/89) for postoperative hemorrhage of grade B and C,4.5% (4/89) for delayed gastric emptying,6.7% (6/89) for deep vein thrombosis,3.4% (3/89) for reoperation,4.5% (4/89)for hospital mortality,7.9% (7/89) for 90-day mortality. The pathological type was pancreatic cancer for all 89 cases and pancreatic ductal adenocarcinoma made up 92.1% (82/89). The tumor size was 4.8(2.0) cm, ranging from 1.5 to 12.0 cm. The number of lymph nodes harvested was 14 (13)(range:2 to 33),with a positive lymph node rate of 13.0% (24.0%). The resection R0 rate was 30.0% (24/80) and the R1 (<1 mm) rate was 58.8% (47/80). The median overall survival time was 21.3 months (95% CI: 15.6 to 24.3) and the median disease-free survival time was 19.1 months (95% CI: 11.7 to 25.1). The overall survival at 1-year and 2-year were 69.60% and 39.52%. The median survival time of 58 patients with adjuvant chemotherapy was 24.3 months (95% CI: 17.8 to 32.3) while that of 13 patients without any kind of adjuvant therapy was 8.4 months (95% CI: 7.3 to 22.3). Seven patients accepted neoadjuvant chemotherapy and there was no significant morbidity among them,with a resection rate of R0 of 5/7. Conclusion:DP-CAR is safe and feasible for selective cases,which could be more valuable in improving long-term survival when combined with (neo) adjuvant therapy.

To determine the types and proportion of common hemoglobin variants in Tianjin and surrounding areas, to analyze the recognition ability and the effects of hemoglobin variants on experimental results in two commonly used glycated hemoglobin systems, so as to provide data support for the consistency of HbA1c detection in Tianjin City. A case-control study was used for retrospective analysis,156 specimens with abnormal electrophoretic peaks in the detection of glycated hemoglobin were collected from more than 50 000 specimens of patients in Chu Hsien-I Memorial Hospital of Tianjin Medical University between June 2020 and December 2020. Determined their hemoglobin mutation sites by DNA sequencing, and compared the values of hemoglobin variants on glycated hemoglobin detection values by high performance liquid chromatography and capillary electrophoresis. SPSS 23 was used to calculate the blood routine results of the variant specimens, and compared with the normal reference interval. The results showed that DNA sequencing identified 21 hemoglobin variants, of which 11 were α strand variants and 10 were β strand variants. In addition, an unreported hemoglobin variant was identified, Hb Headington (HBB: c.217A>C). The HbA_1c of 11 variants including Hb G-Honolulu, Hb Queens, Hb Q-Thailand, Hb J-Broussais, Hb O-Indonesia, Hb G-Coushatta, Hb G-Taipei, Hb E, Hb Headington, Hb New York and Hb D-Los Angeles were shifted by more than 7% when measured by high-performance liquid chromatography. Patients with the Hb Q-Thailand and Hb E cause reduced MCV and MCH. In conclusion, an unreported hemoglobin variant was found from Tianjin and neighboring areas. Patients with the Hb Q-Thailand and Hb E cause reduced MCV and MCH. 11 of these hemoglobin variants interfered with the detection of glycated hemoglobin using high-performance liquid chromatography, resulting in inaccurate results.
Humans ; Glycated Hemoglobin ; Case-Control Studies ; Retrospective Studies ; Hospitals

To determine the types and proportion of common hemoglobin variants in Tianjin and surrounding areas, to analyze the recognition ability and the effects of hemoglobin variants on experimental results in two commonly used glycated hemoglobin systems, so as to provide data support for the consistency of HbA1c detection in Tianjin City. A case-control study was used for retrospective analysis,156 specimens with abnormal electrophoretic peaks in the detection of glycated hemoglobin were collected from more than 50 000 specimens of patients in Chu Hsien-I Memorial Hospital of Tianjin Medical University between June 2020 and December 2020. Determined their hemoglobin mutation sites by DNA sequencing, and compared the values of hemoglobin variants on glycated hemoglobin detection values by high performance liquid chromatography and capillary electrophoresis. SPSS 23 was used to calculate the blood routine results of the variant specimens, and compared with the normal reference interval. The results showed that DNA sequencing identified 21 hemoglobin variants, of which 11 were α strand variants and 10 were β strand variants. In addition, an unreported hemoglobin variant was identified, Hb Headington (HBB: c.217A>C). The HbA_1c of 11 variants including Hb G-Honolulu, Hb Queens, Hb Q-Thailand, Hb J-Broussais, Hb O-Indonesia, Hb G-Coushatta, Hb G-Taipei, Hb E, Hb Headington, Hb New York and Hb D-Los Angeles were shifted by more than 7% when measured by high-performance liquid chromatography. Patients with the Hb Q-Thailand and Hb E cause reduced MCV and MCH. In conclusion, an unreported hemoglobin variant was found from Tianjin and neighboring areas. Patients with the Hb Q-Thailand and Hb E cause reduced MCV and MCH. 11 of these hemoglobin variants interfered with the detection of glycated hemoglobin using high-performance liquid chromatography, resulting in inaccurate results.
Humans ; Glycated Hemoglobin ; Case-Control Studies ; Retrospective Studies ; Hospitals