Objective To investigate the role and mechanism of ubiquitin-specific protease 46 (USP46) in hypoxia/reoxygenation (H/R)-induced pyroptosis of renal tubular epithelial cells. Methods Renal tubular epithelial cells were divided into negative control siRNA group (si-CTL group), USP46 knockdown group (si-USP46 group), negative control siRNA + H/R treatment group (si-CTL+H/R group), and USP46 knockdown + H/R treatment group (si-USP46+H/R group). Flow cytometry was used to detect cell apoptosis in each group. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to measure the messenger RNA (mRNA) expression of USP46, NOD-like receptor protein 3 (NLRP3), gasdermin D (GSDMD), interleukin (IL)-18, and IL-1β. Western blotting was used to detect the protein expression of USP46, NLRP3, GSDMD, and cleaved cysteinyl aspartate specific proteinase (C-Caspase)-1. The levels of inflammatory factors and lactate dehydrogenase (LDH) in the cell supernatants were detected, and the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the cells were detected. Co-immunoprecipitation was used to verify the interaction between USP46 and NLRP3. Results Compared with the si-CTL group, the si-CTL+H/R group exhibited increased cell apoptosis, elevated protein expression of USP46, NLRP3, GSDMD-N and C-Caspase-1, increased mRNA expression of USP46, NLRP3, GSDMD, IL-18 and IL-1β, higher levels of IL-18, IL-1β, TNF-α and LDH, and increased ROS and MDA levels (all P < 0.05). Compared with the si-CTL+H/R group, the si-USP46+H/R group showed decreased cell apoptosis, reduced protein expression of USP46, NLRP3, GSDMD-N and C-Caspase-1, decreased mRNA expression of USP46, GSDMD and IL-18, lower levels of IL-18, IL-1β, TNF-α and LDH, and decreased ROS and MDA levels (all P < 0.05). Co-immunoprecipitation results indicated that USP46 could bind to NLRP3. Conclusions Downregulation of USP46 alleviates H/R-induced pyroptosis in renal tubular epithelial cells, possibly by inhibiting USP46-dependent NLRP3 deubiquitination and promoting NLRP3 ubiquitination and degradation.

In recent years, the rapid development of digital intelligence has provided a new path for rare disease data sharing and injected new power into the progress of research of rare diseases. This research is aimed at summarizing and consolidating relevant literatures on data sharing driven by digital intelligence (DI) in China and abroad, and constructing a local theoretical framework of DI-driven data sharing for rare diseases based on the status of rare diseases in China. Searching PubMed, EMbase, Cochrane, CNKI, Wanfang, and VIP database, we obtain a total of 214 representative literatures. Through literature review, we find that DI technologies have played important roles in different aspects of rare disease data sharing. China, the United States, and Europe have formed their own DI-driven data sharing systems for rare disease. From the theory of " Information Commons", we analyze the gap between China′s current situation and the goal of a " Rare Disease Data Commons". Based on the analysis, we put forward the idea of framework of " DI-STARS". China should develop the Data Sharing system making DI as the core of the system. Meanwhile, China should strengthen the data standardization system, create an innovation-encouraging environment, and build a bridge between different platforms. Using the DI-STARS theory, China will be able to build the " Rare Disease Data Commons" so that the diagnosis and treatment of rare diseases will be enhanced in China to meet the patients′ needs.

ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.

Objective To compare the technical indicators and clinical effect of catheter-directed thrombolysis(CDT)via two types of non-popliteal venous access in the treatment of acute mixed-type lower extremity deep vein thrombosis(DVT).Methods The clinical data of 119 patients with acute mixed-type lower extremity DVT,who were admitted to the Affiliated Jiangning Hospital of Nanjing Medical University and the Affiliated Nanjing Hospital of Nanjing Medical University of China to receive CDT treatment from January 2016 to June 2022,were retrospectively analyzed.Of the 119 patients,CDT via deep calf vein access was carries out in 45(calf vein group)and CDT via healthy-side femoral venous access was performed in 74(femoral vein group).The success rate of vascular puncture,success rate of catheterization technique,number of successful CDT venous puncturing,time spent for sheath placement,time spent for catheterization,thrombolysis time,used amount of thrombolytic agent and associated complications(including vein puncturing and anticoagulant thrombolysis-related complications),the thrombolytic effect of different anatomical segments,and the clinical efficacy during the follow-up period for at least 12 months were compared between the two groups.Results Successful catheterization via deep calf vein access and via healthy-side femoral vein access was obtained in 31 and 58 CDT patients respectively,with a technical success rate of 68.89％(31/45)and 78.38％(58/74)respectively,the difference between the two groups was not statistically significant(P=0.248).In 26 patients(67.74％)of the calf vein group,more than two times of puncturing were needed before the sheath placement could be successfully achieved.The time spent for sheath placement in the femoral vein group was(1.84±0.87)min,which was remarkably shorter than(10.52+6.13)min in the calf vein group(P＜0.001),but the time spent for catheterization in the femoral vein group was(41.60±13.31)min,which was obviously longer than(20.06+4.46)min in the calf vein group(P＜0.001).The thrombolysis time in the femoral vein group and the calf vein group was(5.34+1.43)days and(5.06±1.18)days respectively(P=0.354),and the used amount of thrombolytic agent in the femoral vein group was(352.16±71.98)×104 U,which was prominently larger than(284.68±77.64)× 104 U in the calf vein group(P＜0.001).The last follow-up check showed that the patency rate of the popliteal vein in the calf vein group was significantly higher than that in the femoral vein group(P=0.037).No statistically significant differences in the incidence of post-thrombotic syndrome(PTS)and the mean VEINES-QOL/Sym scores existed between the two groups(all P＞0.05).Conclusion Compared with CDT via healthy-side femoral vein access,CDT via deep calf vein access can better remove the thrombus in the popliteal vein and superficial femoral vein,and improve the femoropopliteal vein patency rate,although it has no obvious advantages in reducing the occurrence of PTS and in improving the VEINES-QOL/Sym score,moreover,the deep calf vein puncture and sheath placement require a high-level technique.

Objective:To compare the clinical efficacy of catheter-directed thrombolysis (CDT) via the contralateral femoral vein approach (CFVA-CDT) and the calf deep vein approach (CVA-CDT) in the treatment of acute mixed-type lower extremity deep vein thrombosis (DVT).Methods:Patients treated with CFVA-CDT and CVA-CDT for acute mixed-type DVT were retrospectively collected from January 2018 to December 2021, totaling 49 and 32 patients, respectively. The relevant technical indicators, thrombolysis rates in the iliac-femoral vein segment and femoral-popliteal vein segment, clinical efficacy, and the incidence of lower extremity deep vein patency, venous valve insufficiency, and post-thrombotic syndrome (PTS), as well as the severity of chronic venous disease in the affected limb (VCSS score) during a 2-year follow-up period were retrospectively compared between the two venous access CDT groups. The t-test was used for comparing quantitative data, while the chi-square test or Fisher′s exact test was used for categorical data.Results:During CFVA-CDT procedure, 6-8 F vascular sheaths were used, and balloon dilation of 2~6 mm was more frequently employed (65.31%, 32/49) to expand venous stenosis/occlusion segments before successful sheath placement compared to the CVA-CDT group (37.50%, 12/32), and the difference was statistically significant ( P=0.014). In the CVA-CDT group, 31.25% (10/32) of patients had a maximum sheath size of 6 F, while the remainder used 4 or 5 F sheaths. Among them, 34.38% (11/32) of patients required re-puncture of the popliteal or femoral vein for larger sheaths (≥8 F) for thrombus aspiration and subsequent endovascular treatment during or after thrombolysis. The effective thrombolysis rates (≥50%) in the iliac-femoral vein segment were not significantly different between the two groups ( P=0.778). The effective thrombolysis rate of the femoral-popliteal venous segment is related to the presence or absence of popliteal vein opacification on lower extremity venous antegrade venography. There was no significant difference between the groups when the popliteal vein was visualized ( P=1.000). While the popliteal vein was not visualized, the CVA-CDT group (75.0%, 15/20) was significantly better than the CFVA-CDT group (34.38%, 11/32), and the difference was statistically significant ( P=0.004). There was no significant difference in clinical efficacy between the two groups ( P=0.819). During follow-up, the femoral-popliteal vein patency rate in the CVA-CDT group (87.50%, 28/32) was significantly higher than in the CFVA-CDT group (44.90%, 22/49), the difference was statistically significant ( P<0.001). Conclusions:Successful CFVA-CDT requires the assistance of more ancillary devices, while the use of larger sheaths is more limited in CVA-CDT due to the smaller caliber of the calf deep veins. The presence or absence of popliteal vein opacification on lower extremity venous antegrade venography may influence the effective thrombolysis of the femoral-popliteal venous segment thrombus in patients with acute mixed deep vein thrombosis (DVT) treated with CFVA-CDT and CVA-CDT. Compared to CFVA-CDT, CVA-CDT can improve the patency rate of the femoral-popliteal venous segment.

Objective:To study the effects of parenteral nutrition containing ω-3 fish oil fat emulsion on the inflammatory status of patients with intestinal fistula at the early stage.Methods:A retrospective analysis was conducted on 28 patients with intestinal fistula who were admitted to the Sixth Department of General Surgery of Anhui Provincial Second People's Hospital from November 2023 to May 2024.The patients were either divided into control group(n=15,parenteral nutrition alone group)or study group(n=13,parenteral nutrition plus ω-3 fish oil fat emulsion)according to whether ω-3 fish oil fat emulsion was added to parenteral nutrition.Both groups of patients received parenteral nutrition support treatment,and the study group was given ω-3 fish oil fat emulsion during treatment.The general information,inflammatory factors in the blood,nutrition,and immune status of two groups of patients were collected and compared.The feces samples on the first and 14th day of admission were collected and analyzed by 16S rRNA high-throughput sequencing of gut microbiota.Results:There was no statistically significant difference in the general information,inflammation,nutrition,immune status,and gut microbiota between the two groups of patients on the first day of admission(P>0.05),indicating comparability between the two groups.After two weeks of parenteral nutrition support,the counts of red blood cells,white blood cells,platelets,lymphocytes,and levels of C-reactive protein,glutamate-pyruvate transaminase,aspartate aminotransferase,total bilirubin,direct bilirubin,total protein,albumin,and creatinine in the research group were similar to those in the control group without statistically significant differences(P>0.05).However,the counts of neutrophils and levels of blood urea nitrogen in the study group were significantly lower than those in the control group(P=0.03 and P=0.01).In addition,the abundance of intestinal flora in the study group was significantly higher than that in the control group(P<0.05).At the genus level,the abundance of Bacteroides_uniformis,Parabacteroides_merdae,Alistipes_finegoldii,Streptococcus_constellatus,Christensenella_minuta were different between the two groups after two weeks of treatment(P<0.05).Conclusion:Parenteral nutrition containing ω-3 fish oil fat emulsion can reduce the counts of neutrophils,which may alleviate inflammatory responses for patients with intestinal fistula at the early stage.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

One patient with kidney stones was prescribed Paishi granules and diclofenac sodium sustained-release tablets for pain relief in the outpatient setting.That evening,the patient took 1 sachet of Paishi granules and 1 diclofenac sodium sustained-release tablet together.The patient subsequently developed a generalized rash with itching.Liver function indexes of alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BiL),direct bilirubin(D-BiL),and alkaline phosphatase(ALP)were all 2 to 6 times higher than the upper limit of normal.After symptomatico treatment,the patients systemic rash had subsided,and the liver function indicators have returned to normal.