Objective: To investigate the influencing factors for delay in healthcare-seeking, definitive diagnosis and identification in patients with pulmonary tuberculosis (PTB) in Minhang District, Shanghai Municipality, so as to provide the basis for effectively reducing delay in PTB patients. Methods: Data of PTB patients in Minhang District from 2017 to 2022 were collected from the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System. The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were analyzed, and factors affecting delay in healthcare-seeking, definitive diagnosis and identification were identified using multivariable logistic regression models. Results: A total of 4 214 PTB patients were reported in Minhang District from 2017 to 2022, including 2 802 males and 1 412 females, with a male-to-female ratio of 1.98∶1. The majority of patients were aged 25 to <45 years (1 664 cases, 39.49%). The prevalence rates of delay in healthcare-seeking, definitive diagnosis and identification were 36.81%, 30.21% and 38.09%, respectively. Delay in healthcare-seeking was associated with the year (2018, OR=0.708; 2019, OR=0.549; 2020, OR=0.670; 2021, OR=0.682), gender (female, OR=1.199), occupation (worker, OR=1.379; housekeeping service/housework/unemployed, OR=1.481), case identification route (symptom-based consultation, OR=11.159), and level of the first-diagnosed hospital (city-level, OR=1.528). Delay in definitive diagnosis was associated with age (45 to <65 years, OR=1.476), occupation (commercial service, OR=0.687; housekeeping service/housework/unemployed, OR=0.672), household registration (non-local, OR=0.820), case identification route (symptom-based consultation, OR=0.616), pathogen test result (negative/not tested, OR=1.903), and the level of the first-diagnosed hospital (city-level, OR=0.311). Delay in identification was associated with the year (2018, OR=0.785; 2019, OR=0.647; 2020, OR=0.790; 2021, OR=0.710), occupation (commercial service, OR=0.687), household registration (non-local, OR=0.848) and level of the first-diagnosed hospital (city-level, OR=0.560) Conclusions Year, gender, occupation, case identification route and level of the first-diagnosed hospital are influencing factors for delay in healthcare-seeking in PTB patients. Age, occupation, household registration, case identification route, pathogen test result and level of the first-diagnosed hospital are influencing factors for delay in definitive diagnosis. Year, occupation, household registration and level of the first-diagnosed hospital are influencing factors for delay in identification.

OBJECTIVE: Rhodiolae Crenulatae Radix et Rhizoma (Hongjingtian in Chinese, RCRR), the roots and rhizomes of Rhodiola crenulata and its application in the medicinal market is very chaotic. In this study, DNA barcoding database and identification engine of Rhodiola species were established, decoction pieces from the medicinal market were identified, and the application and challenges of DNA barcoding in the rapid radiation of Rhodiola species were analyzed. This study provides reference for the protection, rational development, and utilization of endangered resources within Rhodiola species. METHODS: A total of 50 original plant samples from 20 species of the genus Rhodiola from Hebei, Xinjiang, Tibet, Jilin, and other major production areas were collected. Theses samples cover the typical distribution area (Qinghai-Tibetan Platea) of Rhodiola species and other scattered alpine regions (Changbai Mountain, Taibai Mountain, Lushan Mountain, etc.), it encompasses all Rhodiola species with thick rhizomes in China. ITS2 and psbA-trnH barcode of Rhodiola database (BORD) were established and an identification engine named Rhodiola-IDE was developed. The stability and accuracy of the standard DNA barcoding database were evaluated using two datasets. Rhodiola-IDE identified 31 decoction pieces of RCRR from the medicinal material market. RESULTS: The BORD containing 1 532 sequences of 88 Rhodiola species has been established, and the identification efficiency results showed good accuracy and stability. According to the Chinese Pharmacopoeia (2020 edition), 23 samples (74.2%) were identified as authentic R. crenulata, while the rest of the marketed varieties were R. kirilowii, R. dumulosa, and R. fastigiata. The product label "Larger flower, Hongjingtian" was identified as R. crenulata. Samples labeled as "Smaller flower, Hongjingtian" were identified as R. crenulata, R. kirilowii, and R. fastigiata. CONCLUSION ITS2 and psbA-trnH barcodes can identify monophyletic groups represented by R. crenulata. However, for non-monophyletic species, it is necessary to collect as many samples as possible and combine them with multiple markers for joint identification. This study discussed the application and challenges of DNA barcodes in Rhodiola under rapid radiation conditions, providing a scientific basis for the rational development and utilization of Rhodiola varieties.

Objective To analyze the clinical and MR characteristics of fibroadenoma(FA)and phyllodes tumor(PT)with maxi-mum diameter≥5 cm.Methods A total of 33 cases with FA and 34 cases with PT were selected,and all lesions with maximum diameter≥5 cm were confirmed by surgical pathology.The clinical and MR characteristics were analyzed retrospectively.Results PT and FA with tumor maximum diameter≥5 cm were more common in perimenopausal women[(47.35±11.36)years old vs(49.42±11.73)years old,P>0.05],while the FA patient was with the wider age range(19-79 years old).There was statistically significant difference in tumor maximum diameter between PT group and FA group(P<0.001),and tumor maximum diameter of PT group(median 7.06 cm,tumor maximum diameter 17.3 cm)was significantly larger than that of FA group.Coarse calcification was more common in the FA group compared to the PT group(5 vs 0,P=0.011).High signal on T1WI was more common in PT group rela-tive to FA group(50%vs 9.1%,P<0.001).There were no significant differences between the two groups in four characteristics,including tumor margin lobulation(97.1%vs 81.8%),T2WI low signal separation(32.4%vs 30.3%),fibroglandular tissue(FGT),and background parenchymal enhancement(BPE)(P>0.05).Time-signal intensity curve(TIC)of FA group showed typeⅠ and Ⅱ curves,while 4 cases(11.8%)in PT group showed type Ⅲ curves,and there was statistically significant difference in TIC between the two groups(P=0.008).The apparent diffusion coefficient(ADC)values of PT group[(1.48±0.17)×10-3mm2/s]was slightly lower than that of FA group[(1.55±0.20)×10-3 mm2/s],and there was no significant difference in ADC between the two groups(P>0.05).The receiver operating characteristic(ROC)curve showed that the best diagnostic cut-off value for distinguishing between PT and FA with maximum diameter≥5 cm was 6.36 cm,the area under the curve(AUC)was 0.927[95%confidence in-terval(CI)0.860-0.994;P<0.001].The AUC of the T1 WI high signal was 0.705,and the standard error was 0.065(95%CI 0.578-0.831;P=0.004).Conclusion Among FA and PT with tumor maximum diameter≥5 cm,PT appear to be more larger lesion and prone to higher signal intensity on T1WI compared to FA,while coarse calcification is more common in FA.

Diabetic foot(DF)is a common chronic complication in patients with diabetes.Fibrosis and degeneration occurred in fasciae in long term hyperglycemia and inflammatory environment.Fibrosis in fasciae may aggravate the development of diabetic foot due to the special cellular and molecular structure,physiological and biomechanical effects.Thus,we aimed at reviewing the research progress of fascial fibrosis in diabetic foot.

Objective To investigate the organic components in cefmetazole sodium butyl rubber clousures for injection and their migration into drugs,and to evaluate the compatibility of pharmaceutical butyl rubber clousures with cefmetazole sodium.Methods The structures of volatile components in butyl rubber clousures of cefmetzole sodium for injection and those migrated into drugs were identified by GC/MS SCAN mode and National Institute of Standard and Technology(NIST)spectrum library.An HPLC method was established to quantitatively analyse the antioxidants and vulcanizing agents transferred from butyl rubber clousures into drugs.Results Organic compounds such as antioxidant BHT and silicone oil were identified by GC/MS.The HPLC was used to determine the peak area of antioxidant(168,264,330,1 076,1 010)and vulcanizing agent in the range of 0.5-100 μg·mL-1 with good linear relationship with the peak area.The average recoveries(low,medium,and high)of antioxidant and vulcanizing agents ranged from 90.0%to 110.0%,and the corresponding RSD were all less than 2%(n=9).It was found that the antioxidant BHT and silicone oil in cefmetazole sodium butyl rubber clousures for injection would migrate into the drug and affect the clarity of the solution.Conclusion GC-MS/HPLC method can be used as an effective method for quality control of packing materials(butyl rubber clousures)and drug compatibility studies,so as to ensure the safety of drug use by the public.

OBJECTIVES: This study aimed to explore the functions and potential regulatory targets of local macrophages in nonalcoholic fatty liver combined with Porphyromonas gingivalis (P. gingivalis)infection. METHODS: Single-cell RNA sequencing was used to analyze the phenotypes and functional changes in various cells in the liver tissue of nonalcoholic steatohepatitis (NASH) mice fed with P. gingivalis. Real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and immunofluorescence staining were applied to observe the inflammation and expression levels of macrophage antigen presenting functional markers in the NASH liver. Oil red staining was performed to observe the accumulation of local adipose tissue in the NASH liver. Results were verified through RT-PCRand RNA sequencing using P. gingivalis-lipopolysaccharide treated mouse peritoneal macrophages. RESULTS: In comparison with healthy livers with Kupffer cells, the NASH liver combined with P. gingivalis infection-related macrophages showed significant heterogeneity. C1qb, C1qc, Mafb, Apoe, and Cd14 were highly expressed, but Cd209a, H2-Aa, H2-Ab1, and H2-DMb1, which are related to the antigen presentation function, were weakly expressed. Further in vivo and in vitro investigations indicated that the activation and infiltration of these macrophages may be due to local P. gingivalis-lipopolysaccharide accumulation. CONCLUSIONS P. gingivalis-lipopolysaccharide induces a local macrophage immunotolerance phenotype in nonalcoholic fatty liver, which may be the key mechanism of periodontitis pathogen infection that promotes NASH inflammation and pathogenesis. This study further clarifies the dysfunction and regulatory mechanisms of macrophages in the pathogenesis of P. gingivalis-infected NASH, thereby providing potential therapeutic targets for its clinical treatment.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/pathology* ; Kupffer Cells/pathology* ; Porphyromonas gingivalis ; Lipopolysaccharides/metabolism* ; Inflammation/pathology* ; Macrophages/metabolism* ; Mice, Inbred C57BL

Periodontitis is caused by overactive osteoclast activity that results in the loss of periodontal supporting tissue and mesenchymal stem cells (MSCs) are essential for periodontal regeneration. However, the hypoxic periodontal microenvironment during periodontitis induces the apoptosis of MSCs. Apoptotic bodies (ABs) are the major product of apoptotic cells and have been attracting increased attention as potential mediators for periodontitis treatment, thus we investigated the effects of ABs derived from MSCs on periodontitis. MSCs were derived from bone marrows of mice and were cultured under hypoxic conditions for 72 h, after which ABs were isolated from the culture supernatant using a multi-filtration system. The results demonstrate that ABs derived from MSCs inhibited osteoclast differentiation and alveolar bone resorption. miRNA array analysis showed that miR-223-3p is highly enriched in those ABs and is critical for their therapeutic effects. Targetscan and luciferase activity results confirmed that Itgb1 is targeted by miR-223-3p, which interferes with the function of osteoclasts. Additionally, DC-STAMP is a key regulator that mediates membrane infusion. ABs and pre-osteoclasts expressed high levels of DC-STAMP on their membranes, which mediates the engulfment of ABs by pre-osteoclasts. ABs with knock-down of DC-STAMP failed to be engulfed by pre-osteoclasts. Collectively, MSC-derived ABs are targeted to be engulfed by pre-osteoclasts via DC-STAMP, which rescued alveolar bone loss by transferring miR-223-3p to osteoclasts, which in turn led to the attenuation of their differentiation and bone resorption. These results suggest that MSC-derived ABs are promising therapeutic agents for the treatment of periodontitis.
Humans ; Osteoclasts ; Alveolar Bone Loss/therapy* ; Cell Differentiation ; MicroRNAs ; Periodontitis/therapy* ; Extracellular Vesicles ; Apoptosis ; Mesenchymal Stem Cells

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

Objective:To evaluate a self-designed intelligent robot-assisted minimally invasive reduction system in the reduction of unstable pelvic fractures by a cadaveric anatomic study.Methods:Ten unembalmed cadavers (7 male and 3 female ones) were used in this study. In each cadaveric specimen an unstable pelvic fracture was created in accordance with clinical case models (3 cases of type B1, 4 cases of type B2 and 3 cases of type C1 by the Tile classification). A self-designed intelligent robot-assisted minimally invasive reduction system was used to assist the reduction in the cadaveric models. Intraoperative registration and navigation time, autonomous reduction time, total operation time and reduction error were measured.Results:Effective reduction was completed in 10 bone models with the assistance of our self-designed intelligent robot-assisted minimally invasive reduction system. The time for intraoperative registration and navigation averaged 47.4 min (from 32 to 74 min), the autonomous reduction time 73.9 min (from 48 to 96 min), and the total operation time 121.3 min (from 83 to 170 min). The reduction error averaged 2.02 mm (from 1.67 to 2.62 mm), and the reduction results met the clinical requirements.Conclusion:Our self-designed intelligent robot-assisted minimally invasive reduction system is a new clinical solution for unstable pelvic fractures, showing advantages of agreement with clinical operative procedures, high reduction accuracy and operational feasibility, and reduced radiation exposure compared to a conventional operation.

For the past few years, viral diseases such as Coronavirus Disease 2019, Influenza, and Ebola hemorrhagic fever have become more severe and more frequent. For people’s health and the stable operation of the national economy, it is of increasing importance to research the pathogenesis of virus and host immune regulation mechanism, analyze the regulation of gene expression between virus and host, and surveil pathogenic viruses and prevent virus diseases. Transcriptome sequencing is a kind of technology at the RNA level that focuses on the expression characteristics of genes in a specific space-time state, and it is an indispensable tool for analyzing differential gene expression and researching differential splicing of mRNA. With the progress of molecular biology experimental technology and the maturity of bioinformatics analysis platforms, transcriptomics is developing towards the low-cost and low technical threshold, which is gradually transitioning from the research field to the clinical laboratory and changing the traditional cognition of clinical staff in viruses and viral diseases. It has been increasingly used in the research of viral transcription mechanisms, immune interaction between virus and host, tracking disease progression, and antiviral drug development. In order to provide a methodological reference for the research of virus mechanism and prevention and control of virus disease, here, we mainly review meta-transcriptome from three aspects: technical process, common software and application scenarios of virus and virus diseases, and briefly mention the method and applications of other transcriptomes, including a population of cells RNA sequencing (Bulk RNA-seq), Single-cell RNA sequencing (ScRNA-seq), Single-nuclear RNA sequencing (SnRNA-seq), and Spatial Transcriptome (ST).