Objective Genetic testing and prenatal diagnosis were conducted in 18 congenital insensitivity to pain with anhidrosis(CIPA)families,laying the foundation for reducing the incidence of CIPA.Methods Genetic testing was performed using whole-genome sequencing and/or PCR-Sanger sequencing to identify candidate patho-genic vari-ants in the probands.For deep intronic variants,the pathogenicity was validated through minigene assays,RT-PCR,Sanger sequencing,and co-segregation analysis.DNA extracted from chorionic villus or amniotic fluid cells was analyzed by PCR and Sanger sequencing to determine the genotype of the fetuses.Maternal DNA contamination was excluded by microsatellite allele genotyping.Additionally,multiplex ligation-dependent probe amplification(MLPA)was employed to detect common chromosomal aneuploidies.Results A total of 21 NTRK1 variants were identified across 18 CIPA pedigrees,including 9 missense variants,2 nonsense variants,5 frameshift variants,and 5 deep intronic variants.Among them,3 were novel pathogenic variants.Prenatal genetic diagnosis was performed in 20 high-risk fetuses,revealing 2 normal fetuses,12 carriers,and 6 affected with CIPA.Microsatellite genotyping confirmed the absence of maternal DNA contamination in fetal samples.Moreover,MLPA analysis excluded common chromosomal aneuploidies associated with syndromic conditions in all tested fetuses.Conclusions This study achieved a 100%molecular diagnosis rate in CIPA families,identified three novel pathogenic variants,and enabled the simultaneous prevention of CIPA and common chromosomal syndromes through integrated prenatal ge-netic testing,thereby providing critical insights for genetic counseling.

Objective:To investigate the use of computed tomography (CT) and magnetic resonance imaging (MRI) in diagnosing primary retroperitoneal tumors.Methods:The study included 100 patients suspected of having primary retroperitoneal tumors, who were admitted to Xidian Group Hospital between February 2017 and February 2023. All patients underwent pathological biopsy, with the pathological diagnosis serving as the "gold standard." Additionally, each patient underwent both CT and MRI examinations. The diagnostic value of CT and MRI alone or in combination for primary retroperitoneal tumors was compared. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of CT and MRI alone or in combination for primary retroperitoneal tumors.Results:Among the 100 patients with suspected primary retroperitoneal tumors, 90 were pathologically diagnosed with primary retroperitoneal tumors. These included 21 cases of liposarcoma, 18 of schwannoma, 17 of malignant lymphoma, 14 of malignant fibrous histiocytoma, 12 of leiomyoma, and 8 of lipoma. CT confirmed 81 positive cases, MRI confirmed 83 positive cases, and the combined CT and MRI diagnosis identified 89 cases as positive. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of the combined CT and MRI diagnosis for primary retroperitoneal tumors were 98.9% and 90.0%, respectively, with an area under the curve of 0.944, which was superior to that of either CT or MRI alone.Conclusions:CT and MRI play a crucial role in the diagnosis of primary retroperitoneal tumors. The combined use of these two imaging techniques significantly improves both the sensitivity and specificity of diagnosis.

Objective:To investigate the use of computed tomography (CT) and magnetic resonance imaging (MRI) in diagnosing primary retroperitoneal tumors.Methods:The study included 100 patients suspected of having primary retroperitoneal tumors, who were admitted to Xidian Group Hospital between February 2017 and February 2023. All patients underwent pathological biopsy, with the pathological diagnosis serving as the "gold standard." Additionally, each patient underwent both CT and MRI examinations. The diagnostic value of CT and MRI alone or in combination for primary retroperitoneal tumors was compared. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of CT and MRI alone or in combination for primary retroperitoneal tumors.Results:Among the 100 patients with suspected primary retroperitoneal tumors, 90 were pathologically diagnosed with primary retroperitoneal tumors. These included 21 cases of liposarcoma, 18 of schwannoma, 17 of malignant lymphoma, 14 of malignant fibrous histiocytoma, 12 of leiomyoma, and 8 of lipoma. CT confirmed 81 positive cases, MRI confirmed 83 positive cases, and the combined CT and MRI diagnosis identified 89 cases as positive. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of the combined CT and MRI diagnosis for primary retroperitoneal tumors were 98.9% and 90.0%, respectively, with an area under the curve of 0.944, which was superior to that of either CT or MRI alone.Conclusions:CT and MRI play a crucial role in the diagnosis of primary retroperitoneal tumors. The combined use of these two imaging techniques significantly improves both the sensitivity and specificity of diagnosis.

Objective To explore the prognostic value of the coronary angiography-derived index of microcirculatory resistance(caIMR)for major adverse cardiovascular events(MACE)in patients with acute ST-segment elevation myocardial infarction(STEMI)after primary percutaneous coronary intervention(PCI).Methods Between September 2019 and March 2022,541 patients diagnosed with STEMI at the Affiliated Hospital of Xuzhou Medical University were enrolled.The caIMR was calculated using the FlashAngio system(Suzhou Rainmed Medical Technology Co.,Ltd.).The patients were divided into MACE and non-MACE groups according to the occurrence of MACE during hospitalization or follow-up,with MACE defined as all-cause mortality,heart failure readmission,and unplanned revascularization.COX regression analysis,receiver operating characteristic(ROC)curves,and Kaplan-Meier survival curves were used to evaluate the prognostic value of caIMR for STEMI patients after primary PCI.Results During the 1-year follow-up,61 patients(11.28％)experienced MACE.The patients in the MACE group had higher caIMR values than those in the non-MACE group.Multivariate COX analysis showed that caIMR was an independent risk factor for MACE.ROC curve analysis showed that caIMR predicted MACE with an area under the curve of 0.688,and the optimal cutoff value was 25.3 U.caIMR significantly increased the discriminant and reclassification indexes when added to a model with clinical risk factors.The patients were further divided into a low caIMR group(caIMR＜25 U,n=377)and a high caIMR group(caIMR ≥25 U,n=164).Kaplan-Meier curve showed that patients with caIMR≥25 U had a worse prognosis.Conclusions caIMR is an independent risk factor for poor prognosis after PCI in patients with STEMI,and patients with caIMR≥25 U had a worse prognosis.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

Purpose To investigate the difference of resting-state functional connectivity density(FCD)between chronic primary insomnia patients and healthy controls via resting state functional magnetic resonance imaging(rs-fMRI).Materials and Methods All rs-fMRI data of 35 patients with chronic primary insomnia from Xidian Group Hospital and Xi'an Encephalopathy Hospital of Traditional Chinese Medicine,and 35 healthy controls were prospectively collected from August 2020 to December 2021.The voxel-wise FCD approach was applied to explore the differences of whole-brain functional networks between chronic primary insomnia patients and healthy controls.The relationships between FCD value and Pittsburgh sleep quality index,self-rating scale of sleep,insomnia severity index,self-rating anxiety scale and self-rating depression scale in primary insomnia patients were investigated,respectively.Results Compared with healthy controls,the decreased FCD values were showed in the right insula,bilateral anterior cingulate gyrus,left orbitofrontal middle gyrus,left dorsolateral superior frontal gyrus,right medial superior frontal gyrus and bilateral thalamus(t<-5.271,Padjust<0.05),while the increased FCD values showed in the right superior temporal gyrus,bilateral middle temporal gyrus,bilateral precuneus and left posterior cingulate gyrus(t>4.379,Padjust<0.05)in the chronic primary insomnia patients group.The FCD values of bilateral thalamus(r=-0.620,P<0.001;r=-0.562,P<0.005)and right insula(r=-0.651,P<0.001)were negatively correlated with insomnia severity index in the chronic primary insomnia patients group,respectively.Conclusion The extensive functional connectivity abnormalities are observed in primary insomnia patients via FCD analysis.These findings explain the neural mechanisms of underlying emotional regulation and cognitive impairment in chronic insomnia from the perspective of functional integration and functional separation.

Objective:To evaluate the predictive value of prognostic nutritional index (PNI) for survival after radical resection in patients with distal cholangiocarcinoma.Methods:The clinical data of 160 patients with distal cholangiocarcinoma undergoing radical pancreatoduodenectomy in Beijing Chaoyang Hospital Affiliated to Capital Medical University from September 2011 to March 2022 were retrospectively analyzed, including 97 males and 63 females, aged (65.58±9.22) years old. The optimal cut-off value of PNI for predicting postoperative survival was 42.275 determined by the receiver operating characteristic curve. Patients were divided into the low PNI group ( n=79, PNI<42.275) and high PNI group ( n=81, PNI≥42.275). The survival status of patients were followed up by outpatient clinic or telephone review. Survival analysis was performed using the Kaplan-Meier method and the log-rank test. Factors with P<0.1 in the univariate analysis were included in the Cox proportional hazards model for multivariate analysis to screen the prognostic factors. Results:There were statistically significant differences in the preoperative albumin, total bilirubin, lymphocytes counts between the two group (all P<0.05). The postoperative median survival time of the low PNI group was 17 months, with cumulative 1, 3 and 5-year survival rates of 62.0%, 25.0% and 16.2%, respectively. The postoperative median survival time of the high PNI group was 23 months, with cumulative 1, 3 and 5-year survival rates of 84.0%, 46.4% and 40.4%, respectively. There was a significant difference between the two groups ( P<0.001). PNI score<42.275 ( HR=1.040, 95% CI: 1.011-1.071, P=0.008), CA19-9>37 U/ml ( HR=1.620, 95% CI: 1.046-2.509, P=0.031), venous invasion ( HR=1.809, 95% CI: 1.013-3.230, P=0.045), lymph node metastasis ( HR=1.956, 95% CI: 1.300-2.969, P=0.001), tumor diameter >2 cm ( HR=1.534, 95% CI: 1.011-2.328, P=0.044), without postoperative adjuvant chemotherapy ( HR=2.828, 95% CI: 1.291-6.195, P=0.009) had a greater risk of poor survival after radical resection. Conclusion:PNI score could be an influencing factor and serve as a predicting tool for the survival after radical resection in patients with distal cholangiocarci-noma.

OBJECTIVE: To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of treatment efficacy for active ulcerative colitis (UC). METHODS: We retrospectively analyzed the clinical and endoscopic data of 103 patients diagnosed with active UC in Beijing Tsinghua Changgung Hospital from January, 2015 to December, 2020. The severity of endoscopic lesions was determined by Mayo Endoscopic Score and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and the area of the endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification. RESULTS: Univariate analysis suggested that young patients (<40 years old), patients with extensive disease type (E3), patients with high endoscopic scores (MES=3, UCEIS>4, and IMES>4), and patients receiving advanced drug therapy (with systemic hormones, immunosuppressants, immunomodulators, and biological agents, etc.) had lower clinical and endoscopic remission rates. COX survival analysis showed that IMES≤4 was an independent risk factor for clinical and endoscopic remission. ROC curve indicated that the predictive value of IMSE≤4 for clinical and endoscopic remission (AUC=0.7793 and 0.7095, respectively; P<0.01) was better than that of Montreal (AUC=0.7357 and 0.6847, respectively; P<0.01), MES=2 (AUC=0.6671 and 0.5929, respectively; P<0.01), and UCEIS≤4 (AUC=0.6823 and 0.6459, respectively; P<0.01); IMES=5 had a better predictive value for patients with active UC undergoing colectomy tham E3 and MES=3. CONCLUSION IMES has good value in evaluating treatment efficacy for active UC.
Humans ; Adult ; Colitis, Ulcerative ; Retrospective Studies ; Endoscopy ; Immunosuppressive Agents ; Treatment Outcome

Hepatitis B virus core protein (HBc) has become a hot spot in drug carrier protein research due to its natural particle self-assembly ability and ease of modification. The truncation of the C-terminal polyarginine domain (CTD, aa 151-183) of HBc does not affect the self-assembly of the particles. However, it does affect the internal and external charges of the particles, which may subsequently affect drug encapsulation. Thus, the truncated C-terminal polyarginine domain (CTD) of HBc and the inserted RGD peptide were selected to construct and express three HBc variants (RH) encapsulated with ICG (RH/ICG) with different C-terminal lengths to compare the stability and drug activity of their nanoformulations. RH160/ICG was found to have a great advantages in encapsulation efficiency and biological imaging. Compared with other HBc variants, RH160/ICG significantly improved encapsulation efficiency, up to 32.77%±1.23%. Cytotoxicity and hemolysis assays further demonstrated the good biocompatibility of RH160/ICG. Cell uptake and in vivo imaging experiments in mice showed that RH160/ICG could efficiently deliver ICG in tumor cells and tumor sites with good imaging effect. This research provides a new direction for further expanding the diagnosis and treatment application of ICG and development of HBc-based nanoparticle drug carrier platform.
Animals ; Hepatitis B/drug therapy* ; Hepatitis B Core Antigens ; Indocyanine Green/chemistry* ; Mice ; Nanoparticles/chemistry* ; Viral Core Proteins

Phellodendri Chinensis Cortex is perennial deciduous arbors, herbaceous medicinal plants are perennial. It is a rational disposition of Chinese materia medica planting colonies by inter cropping of Phellodendri Chinensis Cortex and herbaceous medicinal plants, based on their different plant height. According to the different demand of sunlight in density and periodicity, the heliophilous and shade-requiring plants, perennial arbors and herbaceous, short and long-term growth plants were intercropping in this kind of the ecological planting pattern. It can efficiently enhance the ecological, economic and social benefits by making full use of nutrients and land sources, as well as increasing the biodiversity in Chinese materia medica planting areas.
Agriculture ; Drugs, Chinese Herbal ; Feasibility Studies ; Materia Medica ; Plants, Medicinal