Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannan-binding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP. Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays. Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05). Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

AIM:To investigate the optimal time of blood collection and the best concentration of Ganlong capsule(GLC)-containing serum for steatohepatitis.METHODS:Sixty C57BL/6J mice were gavaged with GLC at a dose of 90 mg/kg body weight,twice a day for 7 days.Control mice were administered the same volume of 0.9%saline.After 0.5,1,2 and 4 h from the last gavage,blood was collected to prepare GLC-containing serum.The LC-MS/MS was used to detect the inosine content of blank and drug-containing serum at different blood collection times to determine the optimal time.Subsequently,NCTC1469 cells stimulated with palmitic acid(PA)were treated with different concentrations of the GLC-containing serum.Nile Red staining was used to detect lipid droplet formation,and RT-qPCR was employed to as-sess the expression of intracellular fatty acid synthesis(Fabp1,Scd1)and fatty acid β-oxidation gene(Pparα).RE-SULTS:(1)LC-MS/MS detection revealed that the inosine concentration peaked 2 h after the last administration.(2)Nile red staining demonstrated that the GLC-containing serum exerted a dose-dependent decreasing trend of lipid droplets in hepatocytes induced by PA.(3)GLC-containing serum significantly downregulated the mRNA expression levels of lipo-genesis-genes(Fabp1 and Scd1)with a dose-dependent decreasing trend in the PA-induced NCTC1469 cells.The mRNA expression of genes associated with fatty acid β-oxidation(Pparα)were upregulated with a dose-dependent increasing trend.CONCLUSION:The 10%GLC-containing serum collected 2 hours after the last administration in mice has the best therapeutic effect for steatohepatitis.

CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.

The main chemical components of Allii Macrostemonis Bulbus and components in serum were analyzed and identified rapidly and precisely by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)technique in this study.The compounds were identified based on the relative molecular mass,fragmentation ions,and retention time of chromatographic peaks.A total of 36 kinds of chemical components were identified from Allii Macrostemonis Bulbus,including 28 kinds of saponins,3 kinds of amino acids,2 kinds of flavonoids,one kind of organosulfur compound,one kind of nucleoside,and one kind of hormone-lipid compound.In addition,8 kinds of compounds of Allii Macrostemonis Bulbus were identified from the serum.Based on the intersection compounds of which detected in serum and screened out by TCMSP platform database,by using targeted network pharmacology and molecular docking technology,a"drug-component-target-pathway"association network was constructed.Naringenin,quercetin,macrostemonoside E and 25(R)-26-O-β-D-glucopyranosyl-22-hydroxy-5β-furostan-3-O-β-D-glucopyranosyl(1→2)-β-D-glucopyranoside were screened as the main active constituents of Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.In addition,adenosine 5′-monophosphate-activated protein kinase(AMPK),tumor necrosis factor(TNF),vascular endothelial growth factor A(VEGFA)and matrix metallopeptidase 9(MMP9)were the key action targets for Allii Macrostemonis Bulbus in the treatment of hyperlipidemia.Molecular docking was performed using the main pharmacodynamic components and key action targets.The results indicated that all the four active components showed strongly bound to AMPK.This suggested that the regulation of lipid metabolism might be the key mechanism of Allii Macrostemonis Bulbus in antihyperlipidemic effect.This study provided a data reference for the research on the pharmacodynamic components of Allii Macrostemonis Bulbus,and provided a basis for the improvement of quality standard of Allii Macrostemonis Bulbus.

Objective:To investigate the predictive value of the combination of real-time three dimensional echocardiography of esophagus(RT-3D-TEE),computed tomography angiography(CTA)and congestive heart failure hypertension age diabetes mellitus prior stroke or transient ischemic attack vascular disease sex category(CHA2DS2-VASc)for left atrial appendage thrombosis in patients with non-valvular atrial fibrillation.Methods:A total of 88 patients with non-valvular atrial fibrillation admitted to the department of cardiovascular medicine of Cangzhou People's Hospital from January 2022 to June 2023 were selected as the study subjects.They were divided into thrombus group(n=36)and non-thrombus group(n=52)based on whether occurred left atrial appendage thrombosis.All patients underwent RT-3D-TEE and CTA examinations,and underwent CHA2DS2-VASc scoring.Logistic regression was used to analyze the related factors of forming left atrial appendage in patients with non-valvular atrial fibrillation.Receiver operating characteristic(ROC)curve was used to analyze the predictive values of RT-3D-TEE,CTA and CHA2DS2-VASc on left atrial appendage thrombosis in patients with non-valvular atrial fibrillation.And then,area under curve(AUC)value,sensitivity and specificity were calculated.Results:The maximum left atrial appendage emptying velocity(LAAeV)(51.48±5.87),the maximum left atrial appendage filling velocity(LAAfV)(48.36±5.49)and three-dimensional volume ejection fraction(3D-EF)(39.26±3.24)in the thrombus group were all significantly lower than those in the non-thrombus group,and the differences were statistically significant(t=5.933,6.767,4.605,P＜0.05),respectively.The opening diameter,short diameter and circumference,volume and area of left atrial appendage of the thrombus group were all larger than those of the non-thrombus group,while the ejection fraction was smaller than that of the non-thrombus group(t=6.581,3.410,9.220,3.178,4.453,4.162,P＜0.05),respectively.The ratios of cauliflower and cactus types of thrombus group were larger than those of non-thrombus group,and the ratios of wind vane type and chicken wing type were smaller than those of non-thrombus group,and the differences were significant(x2=3.771,7.132,1.003,5.455,P＜0.05),respectively.The CHA2DS2-VASc score of the thrombus group was significantly higher than that of the non-thrombus group,and the difference was statistically significant(t=12.269,P＜0.05).LAAeV,LAAfV,3D-EF,the long diameter of opening,the short diameter of opening,circumference of opening,volume,ejection fraction,spatial morphology and CHA2DS2 VASc score significantly correlated to the left atrial appendage thrombosis of patients with non-valvular atrial fibrillation(OR=4.323-19.562,P＜0.05).The sensitivity,specificity and AUC value of the combination of RT-3D-TEE,CTA and CHA2DS2-VASc were respectively 93.48%,90.83%and 0.895(0.654-0.963)in predicting left atrial appendage thrombosis of patients with non-valvular atrial fibrillation.Conclusion:The predictive values of RT-3D-TEE,CTA and CHA2DS2-VASc are higher for left atrial appendage thrombosis of patients with non-valvular atrial fibrillation.Among of them,the combinations of two or three indicators can effectively improve the predictive efficiency of individual test.The clinical practice should make choice on the basis of actual conditions.

OBJECTIVE To compare the effects of individualized parenteral nutrition versus pre-mixed parenteral nutrition on liver function of patients with acute kidney injury （AKI）. METHODS Totally 97 AKI patients in the intensive care unit of our hospital from January 2021 to March 2022 were collected and randomly divided into pre-mixed multi-chamber bag （MCB） group （48 cases） and compounded parenteral nutrition （COM） group （49 cases）. The patients in both groups were given routine treatment to correct the reversible cause in time， and parenteral nutrition support treatment was started within 48 hours after the fluid resuscitation was successful or the hemodynamics of low-dose vasoactive drugs were stable. MCB group was given one bag of Fat emulsion amino acid （17） glucose （11%） injection， intravenous infusion， once a day； COM group was given Medium/long chain Fat emulsion injection （C8-24Ve） 0.5-0.8 g/kg+Compound amino acid 18AA-Ⅶ 1.0-1.2 g/kg+Glucose injection 1.5-2.5 g/kg+one Water soluble vitamin injection+Fat-soluble vitamin injection （Ⅱ） 10 mL+Multiple trace element injection （Ⅱ） 10 mL+ individualized supplement of sodium chloride and potassium chloride， with a ratio of glucose to lipid of 5∶5 and a ratio of heat to nitrogen of 100∶1. The treatment course of both groups lasted for 7 days. The percentage of abnormal liver function， the levels of liver function indexes [alanine aminotransferase （ALT）， total bilirubin （TBIL）， aspartate transaminase （AST）]， albumin （ALB）， interleukin-6 （IL-6） and C-reactive protein （CRP） were observed in 2 groups before and after treatment. RESULTS After treatment， the ratio of liver dysfunction， the levels of ALT， AST and CRP in MCB group were significantly higher than before treatment； the ratio of liver dysfunction， the levels of ALT and CRP in MCB group were significantly higher than COM group （P＜0.05）. There were no statistical significance in the ratio of liver dysfunction， the levels of ALT， AST， TBIL and CRP in COM group before and after treatment （P＞0.05）. CONCLUSIONS Individualized parenteral nutrition support treatment can reduce the occurrence of liver injury and improve the nutritional status of AKI patients.

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.
Female ; Humans ; Vagina/microbiology* ; Uterine Cervical Neoplasms/genetics* ; Uterine Cervical Dysplasia ; Cervix Uteri ; Lactobacillus/genetics* ; Papillomavirus Infections