OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

To develop a milestone-based evaluation system for the core "knowledge and skills" competency of neurology residents that is tailored to China's medical context, so as to provide precise guidance for their training and assessment.

The bottom-up construction of artificial cells to mimic signal transduction is of great significance for a deep understanding of the communication networks of complex living systems.The dynamic coupling of signal secretion and response among artificial cells poses an important challenge.In this work,two types of artificial cells were constructed through a bio-artificial hybrid strategy.One was an artificial cell as an AI-2 signal sender(sender),which contained bacteria capable of autonomously synthesizing AI-2 signaling molecules.The other was an artificial cell as an AI-2 signal receiver(receiver),which contained bacteria expressing green fluorescent protein in response to the corresponding AI-2 signal.When the ratio of senders to receivers was 4∶1,the fluorescent signal of the receivers gradually increased over time and reached a plateau at 240 minutes.The artificial cells capable of sending and receiving quorum sensing signaling molecules constructed in this work laid a foundation for the study of complex signal communication within artificial cell populations.

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Objective To observe the effects of the traditional Chinese medicine Qingfeihuayutongfu prescription on oxygenation index,respiratory mechanics,inflammatory markers,and immune function in mechanically ventilated patients with sepsis-associated acute respiratory distress syndrome(ARDS).Methods A prospective randomized controlled trial was conducted.Sixty-eight patients with sepsis-associated ARDS,who met the TCM syndrome pattern of lung-heat transferring to intestines syndrome,admitted to the department of intensive care unit(ICU)of the Affiliated Hospital of Nanjing University of Chinese Medicine between January 2023 and January 2024,were enrolled as study subjects.Patients were randomly divided into an experimental group and a control group using a random number table,with 34 patients in each group.Four patients dropped out from each group,resulting in 30 patients being analyzed in each group.Both groups received conventional Western medical treatment after admission.The experimental group additionally received Qingfeihuayutongfu prescription[composition:Scutellaria baicalensis 10 g,Mori Cortex 10 g,Descurainiae Semen 15 g,Trichosanthis Fructus 10 g,Lumbricus 10 g,Persicae Semen 10 g,Salviae Miltiorrhizae Radix 10 g,Curcumae Rhizoma 6 g,Rheum palmatum 3 g(decocted later),Aurantii Fructus Immaturus 10 g,Magnoliae Officinalis Cortex 10 g,Glycyrrhizae Radix praeparata 3 g].The decoction was concentrated to 100 mL per bag.One dose was administered daily,divided into 2 nasogastric feedings.The control group received an equivalent volume of warm water twice daily via nasogastric tube in addition to conventional Western treatment.Treatment continued for 7 days in both groups.Differences in oxygenation index,respiratory mechanics parameters,inflammatory cytokines,and immune cell levels before and after treatment were compared between the two groups.Results Prior to treatment,no statistically significant differences were observed between the two groups in oxygenation index,respiratory mechanics parameters,levels of inflammatory cytokines or immune cell counts.Following treatment,both groups exhibited a significant increase in oxygenation index and natural killer cell(NK cell),alongside significant decreases in plateau pressure(Pplat),driving pressure(ΔP),hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT),interleukins(IL-6,IL-8,IL-1β),tumour necrosis factor-α(TNF-α),and CD4+/CD8+ratio compared to baseline.Post-treatment comparison between groups revealed that the experimental group had a significantly higher oxygenation index and NK cell than the control group[oxygenation index(mmHg,1 mmHg≈0.133 kPa):331.32±90.89 vs.238.64±83.26,NK cell:0.20(0.12,0.25)vs.0.10(0.08,0.19),both P<0.05].Conversely,the experimental group demonstrated significantly lower values than the control group for Pplat,ΔP,hs-CRP,PCT,IL-6,IL-8,TNF-α,CD4+/CD8+[Pplat(cmH2O,1 cmH2O≈0.098 kPa):16(15,19)vs.22(19,24),ΔP(cmH2O):11±2 vs.14±3,hs-CRP(mg/L):21.32(11.63,31.84)vs.41.36(17.41,89.02),PCT(μg/L):0.13(0.08,0.21)vs.0.45(0.14,1.35),IL-6(ng/L):16.25(10.72,49.96)vs.66.70(25.82,195.64),IL-8(ng/L):5.48(0.84,12.60)vs.26.23(23.10,50.16),TNF-α(ng/L):0.77(0.72,1.20)vs.1.10(0.92,1.48),CD4+/CD8+:1.76(1.43,2.00)vs.2.12(1.77,4.03),all P<0.05].Conclusion The Qingfeihuayutongfu prescription can effectively improves the oxygenation index,reduces Pplat and ΔP,mitigates inflammation,and modulates immune function in mechanically ventilated patients with sepsis-associated ARDS.

Objective:To investigate the protective effects of incremental hemodialysis (iHD) combined with furosemide on residual kidney function (RKF) in end-stage renal disease patients who initiate dialysis with preserved RKF.Methods:This was a randomized controlled trial. The patients diagnosed with end-stage renal disease who initiated hemodialysis at the Department of Nephrology, the Affiliated Hospital of Qingdao University from May 2021 to May 2023 were enrolled. The clinical data were collected and analyzed. The patients were randomly assigned to either iHD group (two 4-hour sessions per week or three 3-hour sessions per week, with oral furosemide 40-80 mg twice daily) or the standard HD group (three 4-hour sessions per week, with oral furosemide 40-80 mg twice daily). Differences in clinical characteristics and RKF were assessed between the two groups of patients at 3 months and 6 months, and the differences between the clinical characteristic and the baseline level at 6 months were analyzed, along with the incidence of adverse events.Results:A total of 87 patients met the inclusion and exclusion criteria, of whom 75 completed this study. The mean age was (53.45±12.57) years old, with 37 females (49.33%) and 38 males (50.67%). The patients were assigned to iHD group (39 cases) and standard HD group (36 cases). At 3 months of the trial, compared with standard HD group, the level of serum C-reactive protein was significantly decreased, and the level of eGFR was significantly increased in the iHD group. At 6 months of the trial, the levels of systolic blood pressure, serum β 2-microglobulin, average ultrafiltration volume and C-reactive protein were significantly decreased, and the levels of eGFR, 24-hour urine volume were significantly increased in the iHD group ( P<0.05). The difference in eGFR, urine volume and systolic blood pressure between the iHD group and the baseline level was significantly smaller than that between the standard HD group and the baseline level (all P<0.05). In contrast, the differences in C-reactive protein was significantly greater than that in standard HD group and the baseline level ( P<0.05). At the 3rd, 6th month of the trial, the 24-h urine volumes of iHD group and standard HD group were (955±219) ml/24 h vs. (847±143) ml/24 h, (914±151) ml/24 h vs. (827±124) ml/24 h, showing statistically significant differences ( t=2.510, P=0.014; t=2.729, P=0.008). Adverse events mainly included pulmonary infections (22 cases), fluid overload during the dialysis interval (or more than 5% of the ideal dry weight, 12 cases), heart failure (4R or 4NR grade, 7 cases), hyperkalemia (6 cases), and thrombosis or failure of vascular access (3 cases). The incidence of adverse events did not differ statistically between the two groups ( P>0.05). Conclusion:iHD combined with furosemide helps preserve RKF and maintain urine output within 6 months compared with standard HD in patients with end-stage renal disease.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

This study aims to observe the mind-tranquilizing effect of Fushen Decoction on mice and investigate its effects on the 5-hydroxytryptamine(5-HT) system and γ-aminobutyric acid(GABA) in the brain of the mouse model of 4-chloro-DL-phenylalanine(PCPA)-induced insomnia. ICR mice were administrated with coffee(1 g·kg~(-1)) for 3 days, and the effects of Fushen Decoction(10, 20, and 40 g·kg~(-1)) on the autonomic activities of normal mice and coffee-treated mice were observed. Furthermore, the effects of Fushen Decoction on the autonomic activity and sleep induced by a suprathreshold dose of pentobarbital sodium in the mouse model of PCPA(350 mg·kg~(-1) for 3 consecutive days)-induced insomnia were observed. The levels of tryptophan hydroxylase(TPH), 5-hydroxytryptophan(5-HTP), and 5-HT in the serum, as well as those of 5-HTP and 5-HT in the brain stem, hippocampus, and cortex, were measured by enzyme-linked immunosorbent assay(ELISA). The fluorescence intensity of 5-HT in the raphe nucleus, hippocampus, and cortex was measured by the immunofluorescence method. The protein levels of tryptophan hydroxylase-2(TPH2) and 5-HT_(1A) receptor(5-HT_(1A)R) in the brain stem, hippocampus, and cortex were measured by Western blot. The levels of GABA in the hypothalamus, hippocampus, and cortex were measured by ELISA and immunohistochemistry methods. The results showed that Fushen Decoction(20, 40 g·kg~(-1)) reduced the number of autonomous activities in normal mice, coffee-treated mice, and the mouse model of PCPA-induced insomnia, and prolonged the duration of sleep induced by a suprathreshold dose of pentobarbital sodium in the mouse model. Fushen Decoction(20, 40 g·kg~(-1)) elevated the levels of TPH, 5-HTP, and 5-HT in the serum, and TPH2, 5-HTP, 5-HT, and 5-HT_(1A)R in the brain stem, hippocampus, and cortex, and up-regulated GABA expression in the hypothalamus, cortex, and hippocampus of the mouse model of PCPA-induced insomnia. In conclusion, Fushen Decoction(20, 40 g·kg~(-1)) exerted a mind-tranquilizing effect on mice by up-regulating the expression of TPH2, enhancing the 5-HT system, and elevating the GABA level in the brain.
Animals ; Serotonin/genetics* ; Sleep Initiation and Maintenance Disorders/genetics* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Mice, Inbred ICR ; gamma-Aminobutyric Acid/genetics* ; Disease Models, Animal ; Fenclonine/adverse effects* ; Tryptophan Hydroxylase/genetics* ; Brain/metabolism* ; Sleep/drug effects* ; Humans ; 5-Hydroxytryptophan/metabolism*