Recently， Asian Pacific Association for the Study of the Liver published the recommendations for the diagnosis and management of non-cirrhotic portal fibrosis （NCPF）/idiopathic portal hypertension （IPH）. The guidelines mainly elaborate on the definition， diagnosis， histological features， natural history， and management of NCPF/IPH， in order to strengthen the understanding of NCPF/IPH-related issues and establish a global consensus. This article makes an excerpt of the key statements in the guidelines.

This review systematically summarizes the unique metabolic mechanisms of breast cancer,their interac-tions with the tumor microenvironment(TME),and the latest advances in targeted therapies.The interplay between metabolic reprogramming and the TME underpins malignant progression and therapeutic resistance.Breast cancer cells reshape energy supply through the Warburg effect,aberrant fatty acid synthesis,and amino acid metabolism,while immune cells,fibroblasts,and the acidic milieu within the TME promote immune evasion and drug resistance via metabolic coupling.Although traditional strategies targeting key metabolic enzymes remain valuable,they are often insufficient to overcome metabolic adaptability.In recent years,combined metabolic and immunotherapeutic approaches have emerged as promising strategies:by reducing lactate accumulation,restoring T-cell function,and reprogramming tumor-associated macrophages and cancer-associated fibroblasts,these therapies can remodel the immunosuppressive microenvironment and enhance immunotherapy efficacy.The application of metabolomics and single-cell sequencing further elucidates breast cancer heterogeneity,providing a basis for individualized precision treatment.Future challenges include deciphering resistance mechanisms,developing highly selective metabolic in-hibitors,and designing integrated multi-omics-based therapeutic regimens.

Objective To investigate the predictive value of artificial intelligence-based Alberta Stroke Program Early CT Score(ASPECTS)combined with diffusion-weighted imaging(DWI)cere-bral infarct volume for poor prognosis in wake-up stroke(WUS)patients.Methods A total of 100 patients with acute ischemic stroke after waking up with unknown time window admitted to Kaifeng Cen-tral Hospital from September 2022 to June 2023 were selected as the research objects.All patients un-derwent emergency non-contrast-enhanced cranial CT and magnetic resonance imaging(MRI)scan,followed by reperfusion therapy.The patients were followed up for 3 months after treatment,and were divided into good prognosis[modified Rankin Scale(mRS)≤2]and poor prognosis groups mRS＞2]according to the mRS score.The baseline data,artificial intelligence ASPECTS,and DWI cerebral in-farct volumes were compared between the two groups.Multivariate logistic regression analysis was used to identify prognostic factors,and receiver operating characteristic(ROC)curves were employed to e-valuate the diagnostic efficacy of artificial intelligence ASPECTS combined with DWI cerebral infarct vol-ume.Results After 3 months of follow-up,the poor prognosis rate of patients was 32.00％(32/100).The artificial intelligence ASPECTS at admission in the poor prognosis group was lower than that in the good prognosis group,and the DWI cerebral infarction volume at admission was larger than that in the good prognosis group,with statistically significant differences(P＜0.05).The results of mul-tivariate logistics analysis showed that age(OR=2.190;95％CI,1.412 to 3.398),blood pressure variability(OR=1.726;95％CI,1.192 to 2.500),homocysteine(OR=1.902;95％CI,1.268 to 2.854),D-dimer(OR=2.275;95％CI,1.274 to 4.064),white blood cell count(OR=2.614;95％CI,1.484 to 4.606),neutrophil-to-lymphocyte ratio(OR=2.921;95％CI,1.350 to 6.323),National Institutes of Health Stroke Scale score(OR=3.171;95％CI,1.754 to 5.731),and DWI infarct volume(OR=3.586;95％CI,1.634 to 7.869)were identified as factors affecting poor prognosis(P＜0.05),while high artificial intelligence ASPECTS was identified as a protective factor(OR=0.534;95％CI,0.352 to 0.810;P＜0.05).The sensitivity,specificity and area under the curve of the combined prediction model were 96.88％,85.29％and 0.947,respectively.The sensitivity and AUC of the combined prediction model were higher than that of the single prediction(P＜0.05),and the specificity was similar to that of the single prediction.Conclusion The com-bined application of artificial intelligence ASPECTS and DWI infarct volume significantly enhances predictive efficacy for poor prognosis in WUS patients,providing a more accurate prognostic evalua-tion tool for clinical decision-making,and it has the value of guiding personalized treatment.

OBJECTIVE: To explore the rules of acupoint selection and compatibility of acupuncture and moxibustion in treatment of chronic cough using data mining. METHODS: The ancient and modern medical record cloud platform, and the databases, i.e. CNKI, Wanfang, VIP, EMbase, Web of Science and PubMed, were searched to screen the ancient and modern literature on acupuncture and moxibustion treatment of chronic cough. The prescription database was established for acupuncture and moxibustion treatment of chronic cough, and the analysis conducted on the frequency and use percentage in the aspects of intervention measures, acupoint selection, acupoint distribution, meridian tropism, special points and acupoint combination, as well as the association rules and clustering rules of acupoint selection. The subgroup analysis was performed in accordance with the etiology of chronic cough and intervention measures. RESULTS: A total of 106 articles were included and 158 prescriptions were extracted. The intervention measures were acupuncture, moxibustion, herbal medication and the combination of several measures. The high-frequency acupoints included Feishu (BL13), Zusanli (ST36), Dazhui (GV14), Pishu (BL20), Danzhong (CV17), Shenshu (BL23), Lieque (LU7), Dingchuan (EX-B1), Tiantu (CV22), and Fenglong (ST40). These acupoints are mainly distributed on the back, lumbar region, chest and abdomen. The involved meridians were bladder meridian of foot-taiyang, conception vessel, and lung meridian of hand-taiyin. The special points covered back-shu points, crossing points and five-shu point. Regarding the compatibility of acupoints, the combination of upper and lower points, and the combination of front and back points were predominant in treatment. The analysis of association rules found that the support of Feishu (BL13)→Zusanli (ST36) was the highest; the cluster analysis obtained 8 clusters of acupoints. The acupoint compatibility and overall rules were similar when cough variant asthma (CVA) or the mixed reasons were involved, and the local treatment approach was adopted if the etiology of disease was related to upper airway cough syndrome (UACS) and gastroesophageal reflux cough (GERC). The acupoint selection was similar among different intervention measures. When two kinds of measures were combined in treatment, Feishu (BL13), Pishu (BL20) and Zusanli (ST36) were the most common. CONCLUSION In treatment with acupuncture and moxibustion for chronic cough, the acupoints are selected on the affected local area, depending on syndrome differentiation, and focusing on back-shu points. The main acupoints are Feishu (BL13), Zusanli (ST36), Dazhui (GV14), Pishu (BL20), Danzhong (CV17) and Shenshu (BL23). The combined therapy is dominant with acupuncture, moxibustion and herbal medicine involved.
Acupuncture Points ; Moxibustion/history* ; Humans ; Cough/history* ; Acupuncture Therapy/history* ; Chronic Disease/therapy* ; Data Mining ; History, Ancient ; Meridians ; Chronic Cough

Objective:To analyze the efficacy and safety of different surgical approaches for the treatment of anterior skull base malignancies involving the orbit.Methods:Retrospective analysis was conducted on patients with anterior skull base malignancies involving orbit who attended Xuanwu Hospital of Capital Medical University from April 2013 to July 2021. They were divided into endoscopic endonasal approach(EEA), lateral orbital approach(ELOA), and sublabial transmaxillary approach(ESTMA) groups according to the primary surgical approach. One-way analysis of variance and χ 2 test were used to compare the clinical characteristics, degree of tumour resection, rate of postoperative cranial nerve palsy and improvement of visual acuity; Log-rank test was applied to assess the difference in overall survival (OS). Results:One hundred and ninety-eight patients were enrolled, including 107 males and 91 females, aged (48.5±15.3) years. There were 153, 33, and 12 patients in the EEA, ESTMA, and ELOA groups, respectively. There were no significant differences among the three groups in age, gender, and history of radiotherapy, chemotherapy or surgery ( P>0.05 for all). All patients in ELOA group had preoperative visual impairment (12/12), with a significantly higher percentage than EEA group (56/153) and ESTMA group (14/33) ( χ2=19.72, P<0.001). There was no significant difference between three groups in the degree of tumor resection (gross total resection: 84.97% vs. 81.82% vs. 58.33%, χ2=5.58, P>0.05), postoperative cranial nerve palsy rate (13.07% vs. 30.30% vs. 16.67%, χ2=5.95, P>0.05), visual improvement rate (58.93% vs. 57.14% vs. 58.33%, χ2=0.04, P>0.05) and 5-year OS (60.69% vs. 42.66% vs. 50.00%, χ2=3.22, P>0.05). Conclusion:All three surgical approaches were safe, effective and feasible treatment modalities.

Objective:To analyze the prognostic factors of patients with liver cirrhosis and portal vein thrombosis (PVT), and to construct a prognostic prediction model based on machine learning methods.Methods:The clinical data of 388 patients with liver cirrhosis and PVT admitted to the Fifth Medical Center of PLA General Hospital from January 2022 to April 2024 were retrospectively collected and analyzed, including 243 males and 145 females, aged (56.9±10.9) years. A total of 388 patients were randomly divided into the training set ( n=310) and the testing set ( n=78) in a 4∶1 ratio. The Boruta algorithm was used to screen the key features in the training set, and then four machine learning algorithms, including random forest, support vector machine, generalized linear model and Bayesian, were used to establish a survival prediction model. Model performance was evaluated by the receiver operating characteristic (ROC) curves of the test set and the training set. The patients were followed up for 1 year for survival. Sort the importance of features based on the SHAP value. Results:There were 250 patients (80.6%) who survived and 60 (19.4%) who died. The model for end-stage liver disease score, total bilirubin, serum creatinine, prothrombin time, international normalized ratio, D-dimer, white blood cell count, severe ascites ratio, and Child-Pugh grade C ratio of liver function in the death group were higher than those in the survival group, and the red blood cell count and hematocrit were lower than those in the survival group, and the differences were statistically significant (all P<0.05). The areas under the ROC curve for predicting survival by random forest, support vector machine, generalized linear model and Bayesian model were 0.92, 0.78, 0.81 and 0.71 in the training set, and the area under the ROC curve in the testing set were 0.81, 0.72, 0.67 and 0.68, respectively. Random forest had the best prediction performance, with an accuracy of 81.7%, a sensitivity of 84.6%, and a specificity of 76.9% in the testing set. In the analysis of the importance of characteristic parameters of the random forest model, total bilirubin, red blood cells, hematocrit, serum creatinine, ascites classification, etc. had a relatively high contribution to the model. Conclusion:In the survival prediction model of patients with liver cirrhosis and PVT based on machine learning algorithm, the random forest model had high prediction performance, and total bilirubin may be the most important factor affecting the survival prognosis of patients.

Objective To investigate the effect of lung lobe surface projection localization combined with lung segment drainage sputum technique on airway clearance in patients with aspiration pneumonia,providing a reference for clinical nursing practice.Methods A convenience sampling method was used to select 62 patients with perioperative aspiration pneumonia secondary to brain diseases admitted to a tertiary A hospital in Beijing from May 2022 to October 2024 as the research subjects.A total of 31 patients admitted from August 2023 to October 2024 were assigned to a control group,and 31 patients admitted from May 2022 to July 2023 were assigned to an experimental group.The experimental group received lung lobe surface projection positioning combined with lung segment drainage sputum technique on top of conventional back percussion sputum clearance technique,while the control group received conventional back percussion sputum clearance technique.After the intervention,the differences in oxygenation state,inflammatory test indicators,treatment efficiency,vital signs and frequency of suction coughing between 2 groups were compared.Results After the intervention,the experimental group showed better oxygenation index,frequency of suction coughing,white blood cell count,percentage of neutrophils,procalcitonin levels,interleukin-6 levels,and treatment efficiency compared to those in the control group(P＜0.05).There was no statistically significant difference in heart rate,respiratory rate,and C-reactive protein levels between 2 groups(P＞0.05).Conclusion Lung lobe surface projection positioning combined can effectively promote the patients with aspiration pneumonia of loosening of sputum in the lungs,improve airway clearance efficiency,enhance the patient's pulmonary ventilation and gas exchange capacity,improve oxygenation levels,and reduce systemic inflammatory levels.

Objective:To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province.Methods:A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Approval Number: 2019 Medical Ethics Review No. 67). Results:Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c. 1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c. 467G>A (p.Gly156Asp) and c. 1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c. 1297G>C (p.Ala433Pro) and c. 1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and may affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. Conclusion:The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c. 1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.

Objective:To explore the mechanisms of action of Huanglian Jiedu decoction combined with Xijiao Dihuang decoction (HLJDT-XJDH) in regulating fibroblasts in the treatment of psoriasis. Methods:A mouse model of psoriasis was established by topical application of imiquimod 5% cream on the shaved back; HLJDT-XJDH at different doses of 7.7 and 30.6 g/kg was administered via gavage for intervention, and methotrexate (2 mg/kg) served as a positive control; after 7 days, the severity of skin lesions was assessed using the psoriasis area and severity index (PASI), while histopathological changes of skin tissues were evaluated using hematoxylin-eosin (HE) staining and Baker scoring. For in vitro experiments, fibroblasts were divided into a control group, a model group, a low-dose (5% drug-containing serum) intervention group, and a high-dose (20% drug-containing serum) intervention group; cells in the control group were cultured with 20% normal rat serum for 24 hours; in the model group, cells cultured with 20% normal rat serum were stimulated with 5 ng/ml tumor necrosis factor (TNF) -α and 50 ng/ml interleukin (IL) -17A for 24 hours to mimic fibroblasts during the occurrence of psoriasis; cells in the low- and high-dose intervention groups received the same stimulation as the model group, and were cultured for 24 hours with 5% and 20% HLJDT-XJDH-containing serum, respectively, but not with the 20% normal rat serum. After the above treatment, these cells were co-cultured with keratinocytes (HaCaT cells) using a Transwell system. In addition, on the basis of the control group, fibroblasts were divided into the model group, 20% drug-containing serum intervention group, and 20% drug-containing serum intervention + OE-SFRP2 group; TNF-α and IL-17A were used to stimulate the cells to simulate the psoriatic state; the treatment in the 20% drug-containing serum intervention group was carried out as previously described; in the 20% drug-containing serum intervention + OE-SFRP2 group, cells were transfected with the vector for 48 hours to establish an overexpression model, followed by culture with 20% drug-containing serum for 24 hours, without co-culture with HaCaT cells.. Cell counting kit-8 (CCK-8) assay was performed to assess cell viability, flow cytometry to measure apoptosis rates, enzyme-linked immunosorbent assay (ELISA) to detect levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) as well as chemokine ligand (CXCL) 1 and CXCL12 in mouse serum or cell culture supernatant, qPCR to determine the mRNA expression of inflammatory cytokines, chemokines, cell cycle- and proliferation-related factors, as well as SFRP2 in mouse skin tissues or cells, and Western blot analysis to determine the protein expression of SFRP2, Wnt3a, and β-catenin in fibroblasts. One-way analysis of variance was employed for intergroup comparisons, and post-hoc analysis was conducted using Tukey's test. Results:In vivo mouse experiments showed that compared with the normal control group, the model group exhibited typical psoriatic characteristics in skin morphology, including significant inflammatory infiltration in skin tissues and marked epidermal thickening; compared with the normal control group, the serum levels of TNF-α (531.16 ± 28.27 pg/ml vs. 239.58 ± 10.39 pg/ml), IL-1β (111.40 ± 5.16 pg/ml vs. 80.35 ± 3.87 pg/ml), and IL-6 (109.17 ± 4.84 pg/ml vs. 71.73 ± 2.04 pg/ml) significantly increased in the model group, along with their mRNA expression levels in mouse skin tissues (all P < 0.001) ; compared with the model group, the treatment group showed alleviated psoriatic manifestations, and significant reductions in the levels of inflammatory factors TNF-α (low-dose, high-dose, and positive control groups: 420.80 ± 29.30 pg/ml, 322.33 ± 9.40 pg/ml, 322.97 ± 12.16 pg/ml, respectively), IL-1β (98.69 ± 4.49 pg/ml, 89.02 ± 1.56 pg/ml, 88.88 ± 2.08 pg/ml, respectively), and IL-6 (94.07 ± 3.76 pg/ml, 80.54 ± 3.30 pg/ml, 83.21 ± 3.18 pg/ml, respectively), as well as in their mRNA expression levels (all P < 0.001). In in vitro fibroblast experiments, compared with the control group, the model group exhibited a significant elevation in the supernatant levels of IL-1β (126.42 ± 3.56 pg/ml vs. 34.81 ± 0.44 pg/ml), IL-6 (459.44 ± 9.35 pg/ml vs. 115.51 ± 7.26 pg/ml), CXCL1 (2 434.88 ± 127.63 pg/ml vs. 762.85 ± 30.60 pg/ml) and CXCL12 (3 542.14 ± 35.86 pg/ml vs. 2 095.86 ± 45.12 pg/ml), the expression levels of their mRNAs (all P < 0.001), as well as the protein expression levels of SFRP2, Wnt3a, and β-catenin; after intervention with HLJDT-XJDH-containing serum, all the above indices significantly decreased (all P < 0.001). However, when 20% drug-containing serum intervention was administered simultaneously, the expression of inflammatory factors and chemokines in fibroblasts was significantly higher in the SFRP2 overexpression group than in the non-overexpression group (all P < 0.01). When fibroblasts were co-cultured with HaCaT cells, the model group showed significantly increased cell viability but a decreased apoptosis rate of HaCaT cells compared with the control group, while the low- and high-dose intervention groups showed significantly decreased cell viability but increased apoptosis rates of HaCaT cells compared with the model group (all P < 0.05) . Conclusion:HLJDT-XJDH may exert therapeutic effects in psoriasis by downregulating the SFRP2/Wnt/β-catenin signaling pathway, thereby inhibiting fibroblast activation and inflammatory process, which subsequently suppresses the proliferation of keratinocytes and the activation of inflammatory cells.

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates