Objective:To explore the characteristics of bone marrow morphology and the phenotypic features involved in the flow cytometry (FCM)-based erythroid scoring system in low-risk myelodysplastic syndromes (MDS).Methods:A retrospective case series study was conducted. The clinical data of 13 low-risk MDS patients and 20 non-MDS patients (including 8 cases of iron deficiency anemia, 5 cases of thrombocytopenia, 3 cases of infectious diseases, and 4 cases of leukopenia) collected from outpatient or inpatient samples of multiple hospitals from March 2019 to December 2023 were retrospectively analyzed. The bone marrow morphology examination was performed using Wright-Giemsa staining; the immunophenotypic profiles of erythroblasts were evaluated by FCM; G-banding technique was used to analyze the chromosome karyotypes; next-generation sequencing technology was used for molecular biology detection.Results:Among the 13 low-risk MDS patients, there were 6 males and 7 females, with a median age of 61 years (IQR 15 years). Bone marrow morphological examination showed that the dysplastic hematopoietic morphology of erythroblasts was observed in the bone marrow of 13 low-risk MDS patients, with abnormal nuclear morphology such as odd nuclei, mother-daughter nuclei, petal nuclei, inter-nuclear bridges, multinucleated giants (including abnormal pentanucleated forms), and small megakaryocytes; pathological hematopoiesis in bone marrow accounted for 10%-15% of the erythroblasts system; FCM detection showed that the myeloid primitive cells occupied 0-1.2% of nuclear cells in the bone marrow of low-risk MDS group, expressing CD117, HLA-DR and CD33, partially expressing CD34 and CD38, and not expressing CD19, CD56 and CD7; the developmental pattern of granulocyte CD13/CD16/CD11b was basically normal; partial expression of CD36 and CD71 in erythroblasts was missing. The expression of CD36 and CD71 in erythroblasts of non-MDS group was normal. The expression rates of CD36 in low-risk MDS group and non-MDS group were (51.57±0.13)% and (93.50±0.03)%, respectively ( t = -6.32, P < 0.001), while the expression rates of CD71 were (22.24±0.05)% and (87.94±0.04)%, respectively ( t = -9.47, P < 0.001), with statistically significant differences. The coefficient of variation (CV) of mean fluorescence intensity of CD36 in low-risk MDS group and non-MDS group were 155±8 and 57±10, respectively ( t = 29.18, P < 0.001), and the CV of mean fluorescence intensity of CD71 was 204±33 and 56±6, respectively ( t = 19.43, P <0.001), with statistically significant differences. Among 13 low-risk MDS patients, 4 had abnormal bone marrow chromosome karyotypes, including -7, 8, del(20q), -Y, +15, etc; 5 cases had clonal gene mutations detected by next-generation sequencing, such as ASXL1, SRSF2, TET2, DNMT3A, etc; no 5q-, SF3B1 or TP53 gene mutation was detected. Patients were followed up until December 2023, among the 13 low-risk MDS patients, 7 cases achieved good clinical efficacy, 2 cases transformed into high-risk MDS with excess blasts after 1 year, 3 cases transformed into acute myeloid leukemia M 2 2 years later, and the treatment efficacy of 1 case was unknown. Conclusions:Low-risk MDS patients have pathological hematopoiesis of erythroblasts morphologically. FCM detection shows abnormal developmental patterns of erythroblasts combined with elevated CV of average fluorescence intensity, and often accompanied by genetic abnormalities.

OBJECTIVE: To identify protein markers that may be associated with ulcerative colitis (UC) by analyzing differential proteins in the salivary exosomes from newly diagnosed patients with active UC and healthy controls (HC), and to investigate the function of salivary exosome-specific high-expression proteins in UC patients and their potential role in the pathogenesis of UC. METHODS: All patients and healthy controls were recruited from Peking University People' s Hospital. Whole saliva was obtained from 37 patients with newly diagnosed active ulcerative colitis (n=37) and apparently healthy controls (n=10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The differentially expressed protein genes underwent gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis using the DAVID tool. In vitro, macrophages were co-cultured with salivary exosomes from UC group and those from HC group, respectively, and real-time quantitative polymerase chain reaction (qPCR) was used to detect levels of CD80⁺ and CD86⁺. Additionally, ELISA was performed to measure secretion levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in the cell supernatant. RESULTS: A total of 259 proteins were co-expressed in saliva exosomes from UC group and HC group, among which 11 proteins were highly expressed in the UC group, including PDIA4, A2M, EEF2, C3, PSMA2, PSMB6, PSMA1, IGHG1, IGHG3, IGHG4 and SERPING1, while 4 proteins were lowly expressed in UC group, including TCN1, SLPI and SERPING. Functional analysis of these 15 proteins, along with 129 specific proteins found only in the UC patients and 69 specific proteins found only in HC patients, respectively, was conducted using GO/KEGG. The results revealed that in the UC group, proteasome-related proteins such as PSMA1, PSMA2 and PSMB6 expressions were increased in salivary exosomes while many key molecules involved in complement cascade pathways, such as C3 were up-regu-lated. In vitro co-culture experiments demonstrated that compared with healthy controls, the salivary exosomes of the UC patients in active stage could play a pro-inflammatory role by promoting the transformation of macrophages into M1 type cells that secrete inflammatory factors IL-1β, IL-6 and TNF-α. CONCLUSION Salivary exosomes in the UC patients may have the function of promoting inflammation. Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups. Among them, C3, PSMA2, PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group. These findings suggest that proteins with high specific expression in salivary exosomes of the UC patients have the potential to be used as a disease marker for UC diagnosis and may contribute to the pathogenesis of UC.
Humans ; Colitis, Ulcerative/metabolism* ; Exosomes/metabolism* ; Saliva/metabolism* ; Biomarkers/analysis* ; Male ; Female ; Adult ; Case-Control Studies ; Interleukin-6/metabolism* ; Middle Aged

ObjectiveTo investigate and analyze an outbreak of rotavirus infectious diarrhea in a prison in Chongqing Municipality, to provide a basis for adult rotavirus surveillance and prevention, and to explore the public health problems in special settings. MethodsA retrospective survey was conducted to collect and analyze data on individual cases with diarrheal disease on-site. The clinical characteristics, as well as the temporal, spatial and geographical distribution patterns of the epidemic were described. Multi-pathogen detection tests were conducted both on diarrhea cases and environmental samples, with viral genotyping performed on positive samples. A case-control analysis was performed to identify the causes of the outbreak, and an SEIR model was adopted to predict the outbreak trend and evaluate the effectiveness of interventions. ResultsA total of 65 cases were found among the inmates, with an attack rate of 2.03%. The predominant clinical manifestations included diarrhea (89.23%), watery stool (73.85%), and dehydration (18.46%). The epidemic curve indicated a “human-to-human” transmission pattern, with an average incubation period of 5‒6 days. The attack rates among chefs in the main canteen (80.00%, 8/10) and caterers (28.33%, 17/60) were significantly higher than those of other inmates （P<0.05）. Multi-pathogen polymerase chain reaction (PCR) testing detected positive for group A rotavirus, with the viral genotyping identified as G9P [8] strain. Factors such as unprotected "bare-handed" food distribution among cases with diarrhea (OR=9.512, 95%CI: 4.261‒21.234) and close contact with diarrhea cases (OR=3.656, 95%CI: 1.719‒7.778) were the possible cause of the outbreak. The SEIR model (r₀=5, α=0.3, β₁=0.08, β₂=0.04) was constructed using prison inmates as susceptible population, aiming at fitting the initial transmission trend of the outbreak, and the epidemic rate declined rapidly after intervention measures were implemented (r_t≈0). ConclusionThis rare rotavirus infection diarrhea outbreak among adults in confined settings suggests that the construction of public health prevention and control systems in prison may be overlooked. Cross infection during meal processing and distribution in the canteens of such settings is likely to be the cause of the outbreak. Given the potential neglect of public heath system construction in special settings, it is imperative to enhance the surveillance and monitoring of rotavirus and other intestinal multi-pathogens among adults, as well as the construction of public health prevention and control systems in these special settings.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

The traditional Chinese medicine(TCM) industry is a crucial part of China's pharmaceutical sector and plays a strategic role in ensuring public health and promoting economic and social development. In response to the practical demand for high-quality development of the TCM industry, this paper focused on the bottlenecks encountered during the digital and intelligent transformation of TCM production systems. Specifically, it explored technical strategies and methodologies for constructing the best TCM production mode. An innovative artificial intelligence(AI)-centered technical architecture for TCM production was proposed, focusing on key aspects of production management including process modeling, state evaluation, and decision optimization. Furthermore, a series of critical technologies were developed to realize the best TCM production mode. Finally, a novel AI-driven TCM production mode characterized by a closed-loop system of "measurement-modeling-decision-execution" was presented through engineering case studies. This study is expected to provide a technological pathway for developing new quality productive forces within the TCM industry.
Artificial Intelligence ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional/methods* ; Humans

OBJECTIVE: To evaluate the functional and aesthetic evaluation of external fixator lengthening through plantar approach for fourth brachymetatarsia. METHODS: A retrospective analysis was conducted on 20 patients (23 feet) with fourth brachymetatarsia who met the selection criteria between January 2016 and January 2024, including 3 males and 17 females, with 8 left, 9 right, and 3 bilateral cases. The mean age was 24.7 years (range, 14-51 years). The preoperative metatarsal shortening length was (13.8±3.2) mm. The preoperative American Orthopaedic Foot and Ankle Society (AOFAS) forefoot score was 79.5±3.9, the visual analogue scale (VAS) score of appearance satisfaction was 1.7±0.8, and the appearance index (AI) score was 13.6±0.9. All patients underwent external fixator lengthening through plantar approach. The lengthening length of metatarsal bone, lengthening ratio, healing time, and healing index were recorded. Functional outcomes were assessed using the AOFAS forefoot score, VAS score of appearance satisfaction, and quality-of-life impact with AI questionnaire. RESULTS: All 20 patients were followed up 14-55 months with an average of 36.3 months. During the follow-up, complications occurred in 4 cases (17.4%), including 2 cases of metatarsophalangeal joint stiffness, which had no significant effect on the function and appearance. Delayed union of osteotomy occurred in 1 case (healed at 12 weeks after operation). Pin loosening occurred in 1 case and recovered after outpatient reinforcement. No complications related to plantar scar occurred. At last follow-up, the lengthening length of metatarsal bone was (13.9±3.1) mm, and the lengthening ratio was 25.8%±5.6%. All cases achieved bony union, with a mean healing time of (64.3±12.5) days and a healing index of (46.9±4.8) d/cm. At last follow-up, AOFAS score was 98.9±2.1, the VAS score of appearance satisfaction was 9.3±0.7, and the AI score was 0.6±0.8, which significantly improved when compared with those before operation ( t=27.398, P<0.001; t=32.994, P<0.001; t=56.135, P<0.001). CONCLUSION External fixator lengthening through plantar approach is a safe and effective technique for fourth brachymetatarsia, achieving satisfactory functional and aesthetic outcomes.
Humans ; Male ; Female ; Adult ; External Fixators ; Retrospective Studies ; Bone Lengthening/instrumentation* ; Middle Aged ; Metatarsal Bones/abnormalities* ; Adolescent ; Young Adult ; Treatment Outcome ; Patient Satisfaction ; Esthetics ; Osteotomy/methods* ; Foot Deformities, Congenital/surgery*

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective:To observe the efficacy and safety of combined lienal polypeptide injection therapy in the treatment of Mycoplasma pneumoniae pneumonia（MPP）in children aged 3 to 14 years old in multiple clinical centers.Methods:A randomized，controlled，multi-center clinical study design was adopted.A total of 240 hospitalized children aged 3 to 14 years old with MPP from 7 hospitals from September 1，2023 to January 31，2024 were included.According to the severity of pneumonia，they were divided into the mild MPP group with 80 cases and the severe MPP/refractory MPP（SMPP/RMPP）group with 160 cases，and then randomly divided into the control group and the experimental group at a ratio of 1 ∶1，using the random number table method.After screening，subjects entered a treatment period of 5 to 7 days.The control group was treated with azithromycin，while the experimental group was treated with azithromycin plus lienal polypeptide injection .The recovery of lung CT，length of hospital stay，duration of fever，cough score，whether mild cases developed into severe or refractory cases，duration of hormone use，use of intravenous immunoglobulin（IVIG），bronchoscopy treatment，and immune function were observed between the two groups to evaluate the efficacy of lienal polypeptide injection.Adverse events after medication，vital signs，blood routine，urine routine，liver function，myocardial enzymes，renal function，and electrocardiogram were observed to evaluate the safety. Results:A total of 231 subjects have completed the trial in the 7 hospitals，including 118 cases in the experimental group and 113 cases in the control group.Main observation index：the rate of lung CT aggravation in the experimental group was lower than that in the control group（2.6% vs 15.3%， P<0.01），and the difference was statistically significant.Secondary indexes：there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.However，the rate of cases of plastic bronchitis（PB）found under bronchoscopy in the experimental group was lower than that in the control group（0 vs 18.8%， P=0.03），and the difference was statistically significant.Among the mild MPP（72 cases），there were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and the improvement rate of lung CT between the two groups（all P>0.05）.However，compared with the control group，the rate of cases developing into SMPP/RMPP in the experimental group was less（24.3% vs 48.6%， P=0.03），and the difference in IgG before and after treatment was small［0.53（-0.04，1.18）g/L vs 1.33（0.48，2.25）g/L， P=0.01］.Among the SMPP/RMPP cases（159 cases），the rate of cases of PB found under bronchoscopy in the experimental group was less than that in the control group（0 vs 20%， P=0.04），and the rate of cases with aggravated lung CT in the experimental group was less than that in the control group（1.3% vs 19.5%， P<0.01），and the improvement rate of lung CT in the experimental group was higher than that in the control group（88.8% vs 75.3%， P=0.03），with statistically significant differences.There were no statistically significant differences in the length of hospital stay，duration of fever，cough score，duration of hormone use，whether IVIG treatment was used，the number of bronchoscopy treatment cases，and immunoglobulin between the two groups（all P>0.05）.Two cases in the experimental group developed rashes，which improved after the drug was discontinued.There were no serious adverse reactions such as abnormal vital signs like dyspnea and cyanosis due to the use of lienal polypeptide injection.There were no obvious changes in blood routine，liver function，myocardial enzymes，renal function，electrocardiogram，and urine routine values before and after medication compared with the baseline. Conclusion:The combined use of lienal polypeptide injection in the treatment of MPP in children can reduce the probability of the transformation from mild cases to SMPP/RMPP，reduce the rate of aggravation of the image findings，promote the absorption of lung inflammation，reduce the rate of PB found under bronchoscopy，and has good safety.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.