[Objective] To study the molecular biological mechanism for a case of ABO blood group B subtype, and perform three-dimensional modeling of the mutant enzyme. [Methods] The ABO phenotype was identified by the tube method and microcolumn gel method; the ABO gene of the proband was detected by sequence-specific primer polymerase chain reaction (PCR-SSP), and the exon 6 and 7 of the ABO gene were sequenced and analyzed. Homologous modeling of Bw.03 glycosyltransferase (GT) was carried out by Modeller and analyzed by PyMOL2.5.0 software. [Results] The weakening B antigen was detected in the proband sample by forward typing, and anti-B antibody was detected by reverse typing. PCR-SSP detection showed B, O gene, and the sequencing results showed c.721 C>T mutation in exon 7 of the B gene, resulting in p. Arg 241 Trp. Compared with the wild type, the structure of Bw.03GT was partially changed, and the intermolecular force analysis showed that the original three hydrogen bonds at 241 position disappeared. [Conclusion] Blood group molecular biology examination is helpful for the accurate identification of ambiguous blood group. Homologous modeling more intuitively shows the key site for the weakening of Bw.03 GT activity. The intermolecular force analysis can explain the root cause of enzyme activity weakening.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］

Objective: To evaluate the prevalence and future trend of change of the disease burden of injuries in Chinese children and adolescents from 1990 to 2021, so as to provide reference for injury prevention and control in this population. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021), the trend of change in the disease burden of injuries in children and adolescents in China from 1990 to 2021 was analyzed by the Joinpoint regression model. The Bayesian age period cohort model (BAPC) was used to predict the disease burden of injuries among children and adolescents in China from 2022 to 2031. Results: From 1990 to 2021, the standardized incidence rate, standardized prevalence rate, standardized mortality rate, and standardized disability adjusted life years (DALYs) rate of injuries among children and adolescents in China showed an overall downward trend (AAPC=-1.14%, -0.76%, -5.41%, -5.03%, P <0.05). For different genders, the standardized incidence rate (7 106.00/100 000, 5 388.00/100 000), standardized mortality rate (92.00/100 000, 19.00/ 100 000 ), and standardized DALYs rate (7 834.00/100 000, 1 673.00/100 000) of injuries in boys were higher than the rate of injuries in girls in 1990 and 2021 (5 188.00/100 000, 3 874.00/100 000; 61.00/100 000, 10.00/100 000; 5 398.00/100 000, 945.00/100 000). Compared with Asia and globally, China had the fastest decline in the standardized mortality rate (AAPC= -5.41 ) and the slowest decline in the standardized prevalence rate (AAPC=-0.76) among children and adolescents. The results of the Joinpoint burden trend analysis demonstrated that the standardized incidence rate of injuries showed an increasing trend from 2005 to 2021, and the standardized prevalence rate of injuries showed an increasing trend from 2006 to 2021. Among the different age groups, the disease burden of injuries was highest in the 15-19-year-old group in 2021. For different types of injuries, the standardized incidence rate, standardized mortality rate, and standardized DALYs rate of unintentional injury were higher than those of transport injury, and self harm and interpersonal violence from 1990 to 2021. The BAPC prediction model showed that the standardized incidence rate ( 4 833.05/ 100 000-5 313.70/100 000) and standardized prevalence rate (5 433.90/100 000-5 821.88/100 000) of injury showed an increasing trend, and the standardized mortality rate (13.69/100 000-5.52/100 000) and the standardized DALYs rate ( 1 226.37/ 100 000-510.14/100 000) showed a decreasing trend during 2022-2031. The analysis of influencing factors found that children and adolescents who drank alcohol were at high risk of injury burden. Conclusions From 1990 to 2021, the injury burden of children and adolescents in China generally showed a downward trend. The standardized incidence rate and standardized prevalence rate of injuries are predicted to increase from 2022 to 2031. More targeted and individualized intervention measures should be developed to reduce the injury burden in children and adolescents.

ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Objective: This study aims to explore the association between oral lichen planus (OLP) and Hashimoto’s thyroiditis (HT) and its anti-thyroid antibodies to provide clinical evidence for thyroid disease screening in patients with OLP. Methods: This study was approved by the institutional ethics committee. A total of 125 clinically and histopathologically confirmed patients with OLP were enrolled as the case group, and they were matched with 125 non-OLP controls based on sex and age. Demographic data (gender, age, lesion type, and disease duration) were collected from both groups. Serum levels of thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured to analyze their associations with sex, age, lesion type, and disease duration in patients with OLP. Result: The prevalence of HT in patients with OLP was 31.20%, significantly higher than that in the control group (9.60%) (χ2=18.504, P<0.001). The prevalence of HT in female patients with OLP (39.13%) was significantly higher than that in male patients (9.09%)（χ2=10.93，P<0.001）. The positivity rate of thyroid peroxidase antibodies (TPOAb) in patients with OLP (17.6%) was significantly higher than in the control group (4.0%) (χ2=10.989, P<0.001). The TPOAb positivity rate was significantly higher in female patients (22.83%) than in male patients (3.03%) (χ2=5.210, P=0.014). There was no statistically significant difference in the positivity rate of TgAb between patients with OLP (7.2%) and the control group (3.2%) (P>0.05). Patients with erosive lesions had a significantly higher TPOAb positivity rate (25.0%, 17/68) compared to those with non-erosive lesions (8.77%, 5/57), and the difference was statistically significant (χ2=4.831, P=0.028). Logistic regression analysis revealed that female patients with OLP had an 8.935-fold higher risk of being TPOAb positive compared to males (OR=8.935, 95%CI: 1.134-70.388, P=0.038). Patients with erosive OLP lesions had a 3.199-fold higher risk of TPOAb positivity compared to those with non-erosive lesions (OR=3.199, 95%CI: 1.064-9.618, P=0.038). Conclusion The prevalence of HT is higher in patients with OLP, with higher positivity rates of anti-thyroid antibodies observed in female patients and those with erosive OLP lesions. This suggests that thyroid disease screening should be incorporated into the clinical management of patients with OLP, especially for women and patients who present with erosive lesions.

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats ; Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Serotonin ; Acupuncture Points ; Pain, Referred ; Calcitonin Gene-Related Peptide ; Signal Transduction ; Colitis/therapy* ; Indoles ; Sulfonamides

Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

Objective To summarise the best evidence for postpartum follow-up acquired from patients with gestational diabetes mellitus so as to provide an evidence-based reference for establishment of a postpartum follow-up program.Methods Literature on postpartum blood glucose follow-up in patients with gestational diabetes mellitus was retrieved from 17 major databases including BMJ Best Practice,UpToDate,Joanna Briggs Institute(JBI),International Guide Collaboration Network,National Institute for Health and Care Excellence(NICE),American Diabetes Association website,Medlive,Cochrane Library,Embase,OVID,PubMed,Web of Science,Quanfang local PubMed,CNKI,Wanfang Data,VIP,and Sinomed from the inception of databases to July 2023.The literature to be retrieved included guidelines,expert consensus,evidence summaries,systematic reviews,clinical decisions,and the original studies.Results A total of 9 articles,five practice guidelines,a systematic review,an evidence summaries,an expert consensus and a clinical decisions,were included.Totally,17 pieces of best evidence were summarised from the five aspects:postpartum blood glucose,lifestyle guidance,breastfeeding,drug treatment and health education.Conclusions The summarised best evidences can provide evidence-based references for postpartum follow-up of patients with gestational diabetes.Nursing staff in hospitals and community health centres should formulate relevant follow-up plans according to the actual postpartum conditions of patients in order to prevent the incidence of postpartum Type Ⅱ diabetes.

Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.