Ischemic cholangiopathy （IC） is a severe clinical condition resulting from blood supply impairment in bile ducts， and its etiology includes vascular causes and non-vascular factors. The pathogenesis of IC mainly involves microcirculatory disturbance of the peribiliary blood plexus and biliary epithelial necrosis and fibrosis induced by ischemia-reperfusion injury. The clinical manifestations of IC are highly heterogeneous. The typical symptoms include jaundice， abdominal pain， and cholangitis， while non-specific symptoms， such as fatigue and fever， often cause delays in diagnosis. The diagnosis of IC mainly relies on radiological examination for identifying characteristic stenosis and microcirculatory disturbance， assisted by cholestasis biomarkers including alkaline phosphatase and gamma-glutamyl transferase. Therapeutic strategies include conventional pharmacotherapy， endoscopic intervention， and innovative techniques. Prognostic evaluation emphasizes the dynamic monitoring of alkaline phosphatase and bilirubin and classification based on radiological examination， and long-term management requires individualized monitoring regimens to prevent complications.

BackgroundNon-suicidal self-injury （NSSI） has become a public health concern of wide interest. Adolescents with depressive disorder are at high risk of NSSI behaviors. Previous studies have mostly focused on analyzing factors associated with NSSI behaviors， while research on developing visual models that are intuitive， quantifiable， and suitable for rapid clinical assessment is relatively limited. ObjectiveTo investigate the risk factors for NSSI behaviors in adolescents with depressive disorder， and to construct a nomogram prediction model for the risk of NSSI behaviors occurrence， so as to provide a quantitative tool for clinical rapid assessment of the occurrence risk of NSSI behaviors in this population. MethodsA cross-sectional study was conducted. A total of 448 adolescent patients diagnosed with depressive disorder who attended the Mental Health Department of The Second Hospital， Lanzhou University from February to December 2025 and met the diagnostic criteria for depressive disorder as specified in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were enrolled. All participants were randomly divided into the modeling group （n=313） and the validation group （n=135） at a ratio of 7∶3. Assessments were performed using the Self-rating Depression Scale （SDS）， the Self-rating Anxiety Scale （SAS）， the Barratt Impulsiveness Scale-11 （BIS-11）， the Childhood Trauma Questionnaire-short form （CTQ-SF）， and the Pittsburgh Sleep Quality Index （PSQI）. Binary Logistic regression analysis was applied to screen independent predictors of NSSI behaviors in the modeling group， and a nomogram was constructed accordingly. The receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis （DCA） were used to evaluate the discrimination， calibration and clinical utility of the model， respectively. ResultsBinary Logistic regression analysis revealed that younger age， female sex， higher SDS score， higher BIS-11 score， higher CTQ-SF score， and higher PSQI score were risk factors for NSSI behaviors in adolescent patients with depressive disorder （OR=0.816， 2.671， 1.131， 1.030， 1.064， 1.102， P<0.05 or 0.01）. The Hosmer-Lemeshow test of the nomogram prediction model constructed based on these six indicators showed a good fit （χ²=15.144， P=0.056）. Model validation showed that the AUC was 0.895 for the modeling group and 0.891 for the validation group. The calibration curves suggested that the mean absolute errors between the actual values and the predicted values were 0.043 and 0.023， respectively. Decision curve analysis indicated that the model provided a clear net clinical benefit when the risk threshold was greater than 0.11. ConclusionThe nomogram model based on six indicators （age， sex， depressive symptom severity， impulsivity， childhood trauma， and sleep quality） for predicting NSSI risk in adolescent patients with depressive disorder exhibits good discrimination， calibration， and clinical application value. ［Funded by National Natural Science Foundation of China （number， 82560281）； Gansu Provincial Science and Technology Program （number， 25JRRA618）； Gansu Provincial Health Industry Research Project （number， GSWSKY2025-13）； The College Students' Innovation and Entrepreneurship Training Program of the Second Clinical Medical College of Lanzhou University （number， 20250050060）］

Distal cholangiocarcinoma （dCCA） often has subtle symptoms in its early stage， and the optimal surgical timing is often missed at the time of diagnosis. This article reports a patient with dCCA who attended the hospital due to obstructive jaundice. Although the patient had a history of liver fluke infection and positive serological results， persistent stricture of the common bile duct remained unrelieved after adequate drainage and infection control. Due to the longitudinal growth pattern of the tumor， multiple endoscopic biopsies yielded false-negative results. Multidisciplinary consultation recommended a 1-month follow-up， but the patient failed to return to hospital for review and was found to have liver metastasis （stage Ⅳ） at the time of confirmed diagnosis， and thus the patient missed the opportunity for radical surgery. This article summarizes the common pitfalls and lessons in the early diagnosis of dCCA and proposes that for highly suspected cases in clinical practice， it is crucial to conduct multidisciplinary diagnosis and treatment， integrate dynamic imaging and tumor marker monitoring， and implement proactive structured evaluations， so as to avoid diagnostic and therapeutic delays and ultimately improve the prognosis of patients.

Objective To investigate the role and molecular mechanisms of Exo70 in the metastasis of pancreatic cancer cells. Methods Stable cell lines with Exo70 knockdown or overexpression were established using lentiviral infection. The migration ability of pancreatic cancer cells was assessed by Transwell assay. The morphology, particle size, and secretion levels of exosomes were observed using transmission electron microscopy. Changes in the expression of Exo70 and exosomal marker proteins were detected by Western blot. The localization of multivesicular bodies (MVBs) was examined by immunofluorescence. Results Exo70 knockdown inhibited the migration ability of pancreatic cancer cells and substantially reduced the total amount of exosome secretion. By contrast, Exo70 overexpression enhanced the migration ability of pancreatic cancer cells. Immunofluorescence results showed that Exo70 knockdown induced the perinuclear accumulation of CD63 and LAMP2, leading to an increase in MVB accumulation and lysosomal degradation in pancreatic cancer cells. Conclusion Exo70 promotes the normal transport of MVBs and maintains exosome secretion. Its knockdown enhances the lysosomal degradation of MVBs, resulting in impaired exosome biogenesis and secretion and thereby inhibiting the migration of pancreatic cancer cells.

AIM:To evaluate the effectiveness of EYESI binocular indirect ophthalmoscope simulation system as a training platform for fundus examination skills of general practitioner.METHODS:Prospective randomized study. A total of 40 general practitioners who received clinical ophthalmology training at Shenzhen Eye Hospital from January 2021 to December 2024 were selected and randomly divided into two groups by random number table method, with 20 cases in the study group and 20 cases in the control group. The study group was trained by EYESI binocular indirect ophthalmoscope simulation system and the control group was trained by conventional teaching. Training effects of the two groups were analyzed.RESULTS: The general information of the two groups was comparable. Through training with the EYESI binocular indirect ophthalmoscope simulator, the study group showed significant improvements in total examination and drawing scores compared to pre-training results(all P<0.001). Additionally, examination duration, retinal light exposure time, and drawing time were all significantly shorter than those before training(all P<0.001).The study group achieved significantly higher total examination and drawing scores than the control group during the EYESI binocular indirect ophthalmoscope simulator assessment(all P<0.001). Furthermore, examination duration, retinal light exposure time, and drawing time were all significantly shorter in the study group compared to the control group(all P<0.001). Moreover, ratings for the novelty of the training method and overall satisfaction with the training were significantly higher in the study group than in the control group(all P<0.001); while the perceived psychological stress during training was significantly lower in the study group(P<0.001).CONCLUSION:The EYESI binocular indirect ophthalmoscope simulaton system effectively enhances both the proficiency in fundus examination skills and overall training satisfaction among general practitioners.

Objective:To discuss the effect of prostaglandin E2(PGE2),a pyrogenic mediator,on the discharge activity of warm-sensitive neurons(WSNs)in median preoptic nucleus(MnPO)of hypothalamus in the female mice,and to clarify its mechanism.Methods:Coronal brain slices of MnPO were prepared from the female mice.The slices were then perfused with artificial cerebrospinal fluid(ACSF)containing synaptic transmission blockers(STBs).The discharge frequency was monitored using the patch clamp technique while changing the temperature of the perfusate to identify the WSNs.A total of 32 MnPO WSNs were divided into base line group(n=32)and PEG2(n=32).The patch clamp technique was employed to monitor the discharge frequencies of MnPO WSNs following the perfusion of ACSF and 1 μmol·L-1 PGE2,respectively.The MnPO WSNs with good activity and significant change in discharge frequency after PGE2 perfusion were divided into PGE2 receptor E-series prostaglandin receptrol(EP)1 antagonist(EP1 ant)+PGE2 group(n=7),EP3 ant+PGE2 group(n=7),and EP4 ant+PGE2 group(n=7).The patch clamp technique was used to monitor the discharge frequencies of MnPO WSNs following the perfusion of 3 μmol·L-1 EP1 ant and 1 μmol·L-1 PGE2 mixture,10 μmol·L-1 EP3 ant and 1 μmol·L-1 PGE2mixture,and 10 μmol·L-1 EP4 ant and 1 μmol·L-1 PGE2 mixture,respectively.Resluts:After perfuson of the ACSF containing STBs,a total of 188 MnPO neurons from the female mice with an intrinsic temperature sensitivity coefficient(m value)were identified;out of these,32 neurons had an m value of ≥0.8 and were identified as MnPO WSNs,accounting for approximately 17％of all recorded neurons.Compared with baseline discharge frequency,the discharge frequency of MnPO WSNs after addition of PGE2 was decreased(P＜0.05).Compared with PGE2 group,the percentage change in discharge frequency of MnPO WSNs in EP3 ant+PGE2 group was significantly decreased(P＜0.05).Compared with PGE2 group,the percentage change in discharge frequency of MnPO WSNs in EP1 ant+PGE2 group had no significant difference(P＞0.05).Compared with PGE2 group,the percentage change in discharge frequency of MnPO WSNs in EP4 ant+PGE2 group had no significant difference(P＞0.05).Conclusion:In the female mice,WSNs make up approximately 17％of the total neurons in MnPO.PGE2 can directly inhibit the discharge activity of MnPO WSNs in the female mice through postsynaptic mechanism involving EP3 receptors.

Objective: To investigate the aberrant alterations of microRNAs ( miRNAs) in exosomes derived from bone marrow stromal cells ( BMSCs) in the bone marrow supernatants of patients with acute myeloid leukemia (AML) and their impact on the prognosis of AML patients . Methods: Bone marrow supernatant samples were col- lected from three AML patients and three healthy donors . Exosomes were isolated using a commercial kit , identif- ying the morphology and marker expression , and subjected to miRNA sequencing to determine differentially ex- pressed miRNAs (DE-miRNAs) . The DE-miRNAs were then intersected with the exosomal miRNA expression pro- files of primary AML cells (GSE64029) to exclude AML cell - derived signals and to identify BMSC-derived DE - miRNAs . Subsequently , candidate miRNAs were identified through Cox regression and Lasso regression analyses based on data from The Cancer Genome Atlas (TCGA) . A prognostic risk model for AML was constructed , and pa- tients were stratified into high-risk and low-risk groups according to the median risk score . The prognostic value and clinical relevance of the model were further validated . Finally , the target genes of the candidate miRNAs were pre- dicted , followed by pathway enrichment analysis , construction of key regulatory networks , and correlation analysis between the expression levels of key miRNAs and their corresponding target genes . Results: Isolated exosomes ex- hibited a typical cup-shaped morphology with intact structures with particle size of 30 - 150 nm , and expressed exo- somal markers CD63 , ALIX , and TSG101 . miRNA sequencing identified 103 DE-miRNAs in AML patients com- pared with healthy donors; after intersection with the GSE64029 dataset , 83 BMSC-derived DE-miRNAs were re- tained . Among these , five candidate miRNAs ( miR-25-3p , miR-532-5p , miR-194-5p , miR-10a-5p , and miR- 20a-5p) were used to construct the prognostic model . Kaplan-Meier survival analysis demonstrated significantly lon- ger overall survival in the low-risk group compared with the high-risk group (P < 0. 05) . The areas under the ROC curve for the training/validation cohorts were 0. 80/0. 74 , 0. 80/0. 78 , and 0. 79/0. 64 at 1 , 2 , and 3 years , re- spectively . The prognostic model was significantly associated with risk stratification , patient age , and FAB classifi- cation (P < 0. 05) . KEGG pathway enrichment revealed that target genes of the candidate miRNAs were closely linked to cancer-related signaling pathways , including hepatocellular carcinoma , breast cancer , and non-small cell lung cancer. Correlation analysis indicated that the candidate miRNAs were significantly associated with key genes such as HIF1A , CREB1 , PIK3CA , IGF1R , PIK3R1 , TIAM1 , CRK , and PTEN (P < 0. 05) . Conclusion AML patients exhibit distinct miRNA expression profiles in BMSC-derived exosomes . A five-miRNA signature ( miR-25 - 3p , miR-532-5p , miR-194-5p , miR-10a-5p , and miR-20a-5p) demonstrates robust prognostic performance , sup- porting its potential clinical utility in risk stratification and outcome prediction for AML.

The paper introduces Professor LIU Xing's clinical experience and characteristics of integrative acupuncture and medication in treatment of primary trigeminal neuralgia (PTN). It is believed that the essential pathogenesis of PTN is pathogenic wind, and qi and blood obstruction results from invasion of pathogenic wind. Hence, dispelling wind is the key principle of treatment. Palpation is done at first in the neck, face and buccal mucosal region to detect the masses in treatment. Acupotomy is operated at the masses distributed at Shangguan (GB3), Xiaguan (ST7) and the white line of buccal mucosa, so as to release masses. Additionally, five-wind points (Fengfu [GV16], bilateral Fengchi [GB20], Yifeng [TE17], Bingfeng [SI12] and Fengmen [BL12]), three-nape points (bilateral Naokong [GB19], Tianzhu [BL10] and Jianjing [GB21]) and three-governor-vessel points (Baihui [GV20], Zhiyang [GV9] and Yintang [GV24⁺]) are selected to dispel wind and stop pain. Besides, herbal decoction (wu feng tang) and blood-letting at ear apex are administered in combination. The integration of acupuncture and medication obtains a holistic effect on PTN by dispelling wind pathogen, and promoting qi and blood circulation.
Humans ; Trigeminal Neuralgia/drug therapy* ; Acupuncture Therapy ; Acupuncture Points ; Female ; Male ; Middle Aged ; Drugs, Chinese Herbal/administration & dosage* ; Combined Modality Therapy ; Adult ; Aged

OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction(YQHX)on mitochon-drial midzone division and peripheral fission in myocardial tissue after myocardial infarction(MI).METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group(Sham,n=12)and a left anterior descending coronary ar-tery ligation MI model(n=36).After MI surgery,mice deemed to have successfully developed the model were randomly divided into a model group(MI,n=12),a YQHX group(n=12),and an empagliflozin group(EMPA,n=12)based on echocardiographic results.Four weeks after infarction,cardiac function and structural changes were comprehensively evaluated using echocardiography imaging,serum myocardial injury biomarkers,and hematoxylin-eosin(HE)staining.Transmission electron microscopy(TEM)was employed to observe mitochondrial ultrastructural,morphological,and quantitative changes at the peri-infarct zone.Myocardial mitochondria and cytoplas-mic fractions were isolated from myocardial tissue using a mitochondrial extraction kit,and the spatial expression changes of mitochon-drial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot.These proteins included dynamin-related protein 1(Drp1),its phosphorylated form at serine 616(P-Drp1-Ser616),mitochondrial fission fac-tor(MFF),and mitochondrial fission protein 1(Fis1).RESULTS Compared with the MI group,mice in the YQHX group exhibited sig-nificantly increased left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)(P<0.000 1),as well as decreased left ventricular internal dimension-diastole(LVIDd)and left ventricular end-systolic diameter(LVIDs)(P<0.05,P<0.01),suggesting improved cardiac function.Additionally,serum levels of lactate dehydrogenase(LDH)and creatine kinase-MB(CK-MB)were significantly reduced in the YQHX group(P<0.05,P<0.001),indicating cardio-protective effects of YQHX against ischemic in-jury.HE staining showed that YQHX improved cellular morphology,suggesting structural improvement.TEM showed that YQHX sig-nificantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction,thereby preserving mitochondrial ultrastructure.Furthermore,Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression(P<0.05)in the cytoplasm.Interestingly,YQHX treatment significantly downregulated mitochondrial Fis1 expression(P<0.05),thereby inhibiting peripheral mitochondrial fission.Meanwhile,YQHX treatment significantly increased MFF ex-pression in mitochondria(P<0.01),which may promote mitochondrial midzone fission.CONCLUSION YQHX improves cardiac structure and function after MI,potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial periph-eral fission in ischemic cardiomyocytes.