ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Yttrium-90 selective internal radiotherapy(90Y SIRT)is one of the effective local treatments for inoperable liver malignancies.Catheter-directed CT angiography(CDCTA)involves inserting a catheter into the aimed vessel before CT angiography,hence providing effective cross-sectional images for 90Y SIRT of liver malignancies,helping to ensure the implementation of precise treatment and improve the safety and effectiveness of 90Y SIRT,enormously.The progresses of CDCTA in 90Y SIRT for liver malignancies were reviewed in this article.

Objective:To synthesize hydroxyapatite/poly (lactic-co-glycolic acid)(HA/PLGA) composites by substituting calcium ions in HA with Cu and Gd ions, characterize their physicochemical properties, and evaluate their feasibility for orbital bone defect repair.Methods:Different ratios of Cu-, Gd-, and Cu/Gd-substituted HA nanoparticles (Cu@HA, Gd@HA and Cu/Gd@HA) were synthesized via hydrothermal synthesis using copper nitrate, gadolinium nitrate, calcium chloride, and ammonium hydrogen phosphate.HA/PLGA, Cu@HA/PLGA, Gd@HA/PLGA, and Cu/Gd@HA/PLGA composites were prepared.HA/PLGA was prepared by co-preparing different ratios of nanoparticles with PLGA via phase inversion and solvent evaporation.The nanoparticles and composites were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma (ICP), environmental scanning electron microscope (ESEM) and micro-computed tomography (Micro-CT). Composite homogeneity was assessed by elemental analysis and the contact angle was measured to evaluate hydrophilicity.Imaging capability of composites was assessed by magnetic resonance imaging (MRI) and T1-weighted.CCK-8 method was used to detect the cytotoxicity of nanoparticles and their extract.Orbital bone defects model was established in 20 rats, which were randomly divided into 4 groups, and implanted with respective composites.Eight weeks after transplantation, the implants were evaluated using Micro-CT and MRI, and osteogenesis, collagen distribution and biocompatibility were assessed by hematoxylin-eosin staining, Masson, and Sirius red staining.All animal experiments complied with the regulations of the Laboratory Animal Ethics Committee of Dalian Medical University and were approved (No.AEE23104).Results:XRD and ESEM results showed that co-doping with Cu/Gd induced less HA lattice distortion than single doping.FT-IR results showed that the nanoparticles doped with Cu and Gd ions were consistent with the HA infrared absorption spectrum.ICP results revealed a higher Ca content in 0.5Cu/Gd@HA and 0.5Cu@HA samples than in 0.5Gd@HA sample.There was a statistically significant overall difference in contact angles among different groups of composites ( F=5.040, P<0.05), among which the 0.5Cu/Gd@HA/PLGA composite exhibited the smallest contact angle and the best hydrophilicity.There was no statistically significant difference in porosity among different groups of composites ( F=0.004, P>0.05). MRI results showed that Gd-doped composites displayed enhanced development and that the signal intensity of the 0.5Gd@HA/PLGA group was the highest.Micro-CT scanning results showed that the composition of the composite material doped with Cu and Gd was better than that of the pure HA/PLGA group, indicating that the metal ions Cu and Gd could promote bone growth.CCK-8 results showed that the nanoparticles and their extracts had no obvious cytotoxic effects.Eight weeks after modelling, Micro-CT showed that the 0.5Cu/Gd@HA/PLGA material degraded well in vivo and the staining results of bone tissue sections in the bone defect area suggested that tissues around the implanted material and rat organs in different groups did not show biological toxicity.In addition, the Gd-doped composites showed good magnetic imaging characteristics when implanted in animals. Conclusions:Cu/Gd@HA/PLGA composites exhibit favorable physicochemical properties, biosafety, osteogenic potential, and MRI contrast and have good clinical application prospects for orbital bone repair.

Objective:To synthesize hydroxyapatite/poly (lactic-co-glycolic acid)(HA/PLGA) composites by substituting calcium ions in HA with Cu and Gd ions, characterize their physicochemical properties, and evaluate their feasibility for orbital bone defect repair.Methods:Different ratios of Cu-, Gd-, and Cu/Gd-substituted HA nanoparticles (Cu@HA, Gd@HA and Cu/Gd@HA) were synthesized via hydrothermal synthesis using copper nitrate, gadolinium nitrate, calcium chloride, and ammonium hydrogen phosphate.HA/PLGA, Cu@HA/PLGA, Gd@HA/PLGA, and Cu/Gd@HA/PLGA composites were prepared.HA/PLGA was prepared by co-preparing different ratios of nanoparticles with PLGA via phase inversion and solvent evaporation.The nanoparticles and composites were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma (ICP), environmental scanning electron microscope (ESEM) and micro-computed tomography (Micro-CT). Composite homogeneity was assessed by elemental analysis and the contact angle was measured to evaluate hydrophilicity.Imaging capability of composites was assessed by magnetic resonance imaging (MRI) and T1-weighted.CCK-8 method was used to detect the cytotoxicity of nanoparticles and their extract.Orbital bone defects model was established in 20 rats, which were randomly divided into 4 groups, and implanted with respective composites.Eight weeks after transplantation, the implants were evaluated using Micro-CT and MRI, and osteogenesis, collagen distribution and biocompatibility were assessed by hematoxylin-eosin staining, Masson, and Sirius red staining.All animal experiments complied with the regulations of the Laboratory Animal Ethics Committee of Dalian Medical University and were approved (No.AEE23104).Results:XRD and ESEM results showed that co-doping with Cu/Gd induced less HA lattice distortion than single doping.FT-IR results showed that the nanoparticles doped with Cu and Gd ions were consistent with the HA infrared absorption spectrum.ICP results revealed a higher Ca content in 0.5Cu/Gd@HA and 0.5Cu@HA samples than in 0.5Gd@HA sample.There was a statistically significant overall difference in contact angles among different groups of composites ( F=5.040, P<0.05), among which the 0.5Cu/Gd@HA/PLGA composite exhibited the smallest contact angle and the best hydrophilicity.There was no statistically significant difference in porosity among different groups of composites ( F=0.004, P>0.05). MRI results showed that Gd-doped composites displayed enhanced development and that the signal intensity of the 0.5Gd@HA/PLGA group was the highest.Micro-CT scanning results showed that the composition of the composite material doped with Cu and Gd was better than that of the pure HA/PLGA group, indicating that the metal ions Cu and Gd could promote bone growth.CCK-8 results showed that the nanoparticles and their extracts had no obvious cytotoxic effects.Eight weeks after modelling, Micro-CT showed that the 0.5Cu/Gd@HA/PLGA material degraded well in vivo and the staining results of bone tissue sections in the bone defect area suggested that tissues around the implanted material and rat organs in different groups did not show biological toxicity.In addition, the Gd-doped composites showed good magnetic imaging characteristics when implanted in animals. Conclusions:Cu/Gd@HA/PLGA composites exhibit favorable physicochemical properties, biosafety, osteogenic potential, and MRI contrast and have good clinical application prospects for orbital bone repair.

Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.

OBJECTIVES: To explore the promoting effect of ginsenoside Rb3 (Rb3) on osteogenesis in periodontitis environment, and to explain its mechanism. METHODS: Human periodontal ligament stem cells (hPDLSCs) were cultured by tissue block method and identified by flow cytometry. Cell counting kit-8 (CCK8) method and calcein acetoxymethyl ester/propidium iodide staining were used to detect the effect of Rb3 on the viability of hPDLSCs cells. In vitro cell experiments were divided into control group, 10 μg/mL lipopolysaccharides (LPS) group, 10 μg/mL LPS+100 μmol/L Rb3 group and 10 μg/mL LPS+200 μmol/L Rb3 group. Alkaline phosphatase (ALP) staining was used to detect the ALP activity of hPDLSCs in each group after osteogenesis induction. The expression of hPDLSCs interleukin-6 (IL-6), interleukin-8 (IL-8), runt-related transcription factor 2 (RUNX2) and transforming growth factor-β (TGF-β)genes in each group after osteogenesis was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. Western blot was used to detect the protein expression of hPDLSCs phosphorrylated extracellular signal-regulated kinase (p-ERK) in each group. Sprague-Dawley rats were randomly divided into the control group, ligation group and ligation+Rb3 group. The left molar-maxillary tissue was subjected to micro-computed tomography (micro-CT) scanning. After the scanning, the left molar-maxilla was made into periodontal tissue sections. Hematoxylin-eosin (HE) staining was used to detect the infiltration and loss of adhesion of inflammatory cells. Masson staining was used to detect the destruction of gingival collagen fibers. Immunofluorescence staining was used to detect the protein expression of RUNX2 and p-ERK. The expression of TGF-β in rat gingival tissue was detected by qRT-PCR. The protein expression of IL-6 in peripheral serum of rats was detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of Treg cells in rat heart blood. The experimental data were statistically analyzed by Graph Pad Prism10.1.2 software. RESULTS: Rb3 had no effect on the cell activity of hPDLSCs. The results of qRT-PCR and ALP staining showed that Rb3 could inhibit the gene expression of IL-6 and IL-8 in inflammatory hPDLSCs, promote TGF-β gene and promote the osteogenic differentiation of inflammatory hPDLSCs. Western blot showed that Rb3 inhibited the protein expression of inflammatory hPDLSCs p-ERK. The results from micro-CT, Masson staining, and HE staining demonstrated that Rb3 promotes alveolar bone formation in rats with periodontitis, while simultaneously inhibiting the destruction of periodontal fibrous tissue, reducing attachment loss, and suppressing inflammatory cell infiltration. The results of flow cytometry showed that Rb3 could promote the differentiation of Treg cells in peripheral blood of periodontitis rats. The results of ELISA and qRT-PCR showed that Rb3 could inhibit the protein expression of IL-6 and promote the gene expression of TGF-β in periodontitis rats. Immunofluorescence results showed that Rb3 could promote the protein expression of RUNX2 and inhibit the protein expression of p-ERK in periodontitis rats. CONCLUSIONS Rb3 can reduce the inflammatory reaction of periodontal tissues in periodontitis rats, and promote the osteogenic differentiation of hPDLSCs by regulating p-ERK pathways.
Animals ; Ginsenosides/pharmacology* ; Osteogenesis/drug effects* ; Periodontitis/metabolism* ; Rats ; Periodontal Ligament/cytology* ; Humans ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Stem Cells/drug effects* ; Interleukin-6/metabolism* ; Rats, Sprague-Dawley ; Interleukin-8/metabolism* ; Cells, Cultured ; MAP Kinase Signaling System/drug effects* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Male ; Phosphorylation ; Lipopolysaccharides ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Alkaline Phosphatase/metabolism*

Objective To report cases of checkpoint inhibitor pneumonitis （CIP） in patients with advanced biliary tract cancer, aiming to provide additional approaches for the assessment, treatment, and monitoring of this condition. Methods Three patients developed oxygen desaturation and interstitial lung lesions during chemotherapy combined with immunotherapy, and were diagnosed with CIP in collaboration with the respiratory department. Antitumor therapy was discontinued in the acute phase, and glucocorticoids were administered, with regular monitoring of disease progression. During follow-up, case 1 developed lung metastasis; case 2 showed improvement; case 3 had concurrent infection and tumor progression. Results Glucocorticoids improved lung lesions and hypoxic symptoms in patients with CIP, but attention should be paid to the potential for concurrent infections and tumor progression. Conclusions Comprehensive assessment and early identification of CIP are crucial for patients with advanced biliary tract cancer. For those with recurrent symptoms after glucocorticoid therapy, timely and accurate adjustment of the treatment regimen is essential.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective:The aim of this study was to analyze the registration status of osteoporosis drug clinical trials in China, providing a reference for the research and development of therapeutic drugs for osteoporosis.Methods:Using the Drug Clinical Trial Registration and Information Publication Platform on the website of the State Drug Administration as the search platform, we retrieved the information on the public announcement of drug clinical trials with osteoporosis as an indication, and the search period was limited from 2013 to February 2025.Researchers extracted the key information and performed statistics.Results:A total of 182 registered osteoporosis drug clinical trial projects were collected.The main target indications were predominantly osteoporosis in postmenopausal women, and there were relatively few trials targeting the elderly subjects.56.0%(102/182)of the registered trials were bioequivalence studies, and 21.4%(39/182)were phase I clinical studies.Conclusions:The number of registered trials and the research and development process of domestic osteoporosis drug clinical trials in China have shown a stable trend in general, and the types of trials are mainly concentrated in bioequivalence studies and early clinical studies.In order to further meet the medication needs of domestic patients, China still needs to increase the research and development efforts of innovative osteoporosis drugs.

Objective:To expand the mutation spectrum of familial benign chronic pemphigus (HHD), and to deeply explore the relationship between clinical phenotypes and genotypes.Methods:HHD patients were retrospectively collected from the Department of Dermatology, Hospital for Skin Diseases, Shandong First Medical University from January 2018 to October 2023, and their clinical data and blood samples were also collected. Sanger sequencing and Whole-exome sequencing were performed on 34 HHD patients. Mutations in the ATP2C1 gene were classified into loss-of-function mutations (including frameshift mutations, nonsense mutations, and splicing mutations) and missense mutations. The relationship between clinical phenotypes and genetic mutation types was analyzed using Fisher's exact test or two-independent-sample t test, and further verified by meta-analysis. Results:The 34 HHD patients were all of Chinese Han nationality, including 20 males and 14 females, and their ages ranged from 35 to 77 years. Pathogenic mutations in the ATP2C1 gene were successfully identified in all the 34 patients, including 29 independent mutations, among which there were 9 frameshift mutations, 8 splicing mutations, 6 missense mutations, and 6 nonsense mutations. The age at onset was significantly earlier in the loss-of-function mutation group (37.62 ± 10.10 years) than in the missense mutation group (49.63 ± 14.90 years; t = 2.62, P = 0.013). However, there were no significant differences in gender, family history, disease seasonality, disease severity, or disease progression among patients with different mutation types (all P > 0.05). Meta-analysis showed that the age at onset was significantly earlier in Chinese Han patients with HHD carrying loss-of-function mutations than in those carrying missense mutations (mean difference: -4.61 years, 95% CI: -8.68 - -0.53 years, P = 0.030) . Conclusion:Chinese Han patients with HHD carrying loss-of-function mutations in the ATP2C1 gene showed significantly earlier ages at onset compared with those carrying missense mutations.