OBJECTIVE To investigate the absorption characteristics and tissue distribution of silybin （Sy） nanocrystals prepared by two methods in different intestinal segments of rats. METHODS Sy nanocrystals （i.e. Sy-NS-G and Sy-NS-F） with comparable particle sizes were prepared using high-pressure homogenization and anti-solvent precipitation methods， respectively. Rats were randomly divided into three groups： Sy raw drug group， Sy-NS-G group， and Sy-NS-F group. Each group was further divided into three subgroups with low， medium， and high （60， 120， 180 μg/mL） mass concentrations （calculated based on Sy）， with 3 rats in each subgroup. The absorption rate constant （Ka） and apparent absorption coefficient （Papp） of Sy raw drug， Sy-NS-G and Sy-NS-F in different intestinal segments were investigated by using the in vivo one-way intestinal perfusion experiment. Additionally， the rats were divided into three groups: Sy raw drug group， Sy-NS-G group， and Sy-NS-F group， with 20 rats in each group. Rats in each group were administered a single intragastric dose of 50 mg/kg （calculated based on Sy）. They were sacrificed at 0.3， 1， 4， 10， and 24 hours post-administration respectively， to investigate the tissue distribution of Sy raw drug， Sy- NS-G， and Sy-NS-F in the heart， liver， spleen， lungs， kidneys， brain and intestines. RESULTS In duodenum and jejunum， the Ka and Papp of the nanocrystals prepared by the two methods remained unchanged with the increase of Sy concentration， and there was no significant difference （P＞0.05）； the absorption of Sy-NS-F in the duodenum was greater than that of Sy-NS-G； the absorption sites of Sy-NS-G and Sy raw drug were mainly in the ileum， while those of Sy-NS-F were mainly in the duodenum and ileum. The concentrations of Sy-NS-G and Sy-NS-F in different tissues of rats were different； Sy-NS-G peaked in most tissues at 1 h， and the distribution concentration was as follows： intestine＞spleen＞heart＞lungs＞liver≈brain＞kidneys. Sy-NS-F reached its peak at 1 h， and the distribution concentration was in the order of intestine＞spleen＞kidney＞lung＞heart≈liver＞brain. CONCLUSIONS The absorption mode of Sy nanocrystals in the duodenum and ileum is mainly passive diffusion. In the duodenum， the absorption of Sy-NS-F is greater than that of Sy-NS-G； there are significant differences in the tissue distribution of Sy-NS-G and Sy-NS-F in rats.

Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

ObjectiveTo systematically evaluate the efficacy and safety of omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy. MethodsThis study was conducted according to the PRISMA guideline. English and Chinese databases including CNKI， Wanfang Data， VIP， CBM， the Cochrane Library， PubMed， Embase， and Web of Science were searched for clinical studies on omental wrapping technique for pancreaticojejunal anastomosis in preventing complications after pancreaticoduodenectomy published up to November 2022， and Stata 16 and Review Manager 5.4 were used to perform the meta-analysis. ResultsA total of 15 studies with 1 830 patients were included in this study. The meta-analysis showed that the omental wrapping group had a significantly lower overall incidence rate of postoperative pancreatic fistula （POPF） than the non-omental wrapping group （odds ratio ［OR］=0.30， 95% confidence interval ［CI］： 0.22‍ ‍—‍ ‍0.41， P<0.001）， and the subgroup analysis showed that the omental wrapping group had a significantly lower incidence rate of grade B/C POPF than the non-omental wrapping group （OR=0.29， 95%CI： 0.21‍ ‍—‍ ‍0.39， P<0.001）. Compared with the non-omental wrapping group， the omental wrapping group had significantly lower incidence rates of postoperative bile leakage （OR=0.30， 95%CI： 0.16‍ ‍—‍ ‍0.56， P<0.001）， postoperative hemorrhage （OR=0.35， 95%CI： 0.24‍ ‍—‍ ‍0.53， P<0.001）， delayed gastric emptying （OR=0.45， 95%CI： 0.31‍ ‍—‍ ‍0.64， P<0.001）， abdominal infection （OR=0.55， 95%CI： 0.40‍ ‍—‍ ‍0.75， P<0.001）， reoperation （OR=0.31， 95%CI： 0.18‍ ‍—‍ ‍0.54， P<0.001）， and death within 30 days after surgery （OR=0.42， 95%CI： 0.22‍ ‍—‍ ‍0.80， P=0.009）， a significantly earlier time to diet （mean difference ［MD］=-0.98， 95%CI： -1.84 to -0.11， P=0.03）， and a significantly shorter length of postoperative hospital stay （MD=-2.44， 95%CI： -4.10 to -0.77， P=0.004）. There were no significant differences between the two groups in the time of operation （MD=-13.68， 95%CI： -28.31 to -0.95， P=0.07） and intraoperative blood loss （MD=-17.26， 95%CI： -57.55 to -23.03， P=0.40）. ConclusionOmental wrapping can reduce the incidence rates of postoperative complications such as pancreatic fistula， bile leakage， postoperative hemorrhage， abdominal infection， and delayed gastric emptying， improve the prognosis of patients， and shorten the length of hospital stay， without increasing surgical difficulty or time of operation.

A 79-year male presenting with abdominal distension, diarrhea, edema and oliguria, which soon progressed to acute renal failure, was admitted in Xiamen Branch of Zhongshan Hospital. The diagnosis of atypical hemolytic uremic syndrome (aHUS) was confirmed after admission. The hematological parameters and renal function were improved after prompt hemodialysis, plasma exchange, plasma and immunoglobulin transfusion. The patient experienced multiple recurrences of aHUS within 1 year, but achieved long-term remission with regular use of eculizumab. The reported cases of aHUS were searched from Wanfang Data Knowledge Service Platform and CNKI Database from January 2000 to January 2024, and 64 non-pregnant adult aHUS cases were retrieved from literature. The analysis of 65 cases showed a male-to-female ratio was 1.2∶1 and an average age of 34.8 years ranging from 20 to 86 years. Common clinical manifestations included fever (24 cases, 36.9%), renal dysfunction (27 cases, 41.5%), and neurological symptoms (15 cases, 23.1%). Additionally, 40 cases (61.5%)had concomitant hypertension. Among the 65 patients, 36 (55.4%) received hemodialysis, 31 (47.7%) underwent plasma exchange or plasma transfusion, 29 (44.6%) were treated with glucocorticoids, and only 3 (4.6%) were treated with eculizumab. In terms of treatment outcomes, 29.2% (19 cases)of the patients achieved complete renal function recovery, 46.2% (30 cases)developed end-stage renal disease, and 4 patients died. aHUS presents with a variety of clinical manifestations involving multiple systems. Plasma exchange remains the primary treatment method at present. Early and accurate diagnosis, prompt and effective treatment can significantly improve patient prognosis.

Objective A deep learning-based method for evaluating the quality of pediatric pelvic X-ray images is proposed to construct a diagnostic model and verify its clinical feasibility.Methods Three thousand two hundred and forty-seven children with anteroposteric pelvic radiographs are retrospectively collected and randomly divided into training datasets,validation datasets and test datasets.Artificial intelligence model is conducted to evaluate the reliability of quality control model.Results The diagnostic accuracy,area under ROC curve,sensitivity and specificity of the model are 99.4%,0.993,98.6%and 100.0%,respectively.The 95%consistency limit of the pelvic tilt index of the model is-0.052-0.072.The 95%consistency threshold of pelvic rotation index is-0.088-0.055.Conclusion This is the first attempt to apply AI algorithm to the quality assessment of children's pelvic radiographs,and has significantly improved the diagnosis and treatment status of DDH in children.

Objective:To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants.Methods:This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1 st, 2015 to December 31 st, 2021 of the Seventh Medical Center of the People′s Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children′s Hospital from January 1 st, 2020 to December 31 st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks′ corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model′s discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results:A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95% CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions:A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.
Animals ; Swine ; African Swine Fever Virus/metabolism* ; Membrane Proteins/metabolism* ; Immunity, Innate ; Nucleotidyltransferases/metabolism* ; Signal Transduction/genetics*

In order to understand the prevalence and evolution of porcine reproductive and respiratory syndrome virus (PRRSV) in China and to develop subunit vaccine against the epidemic lineage, the genetic evolution analysis of PRRSV strains isolated in China from 2001 to 2021 was performed. The representative strains of the dominant epidemic lineage were selected to optimize the membrane protein GP5 and M nucleotide sequences, which were used, with the interferon and the Fc region of immunoglobulin, to construct the eukaryotic expression plasmids pCDNA3.4-IFNα-GP5-Fc and pCDNA3.4-IFNα-M-Fc. Subsequently, the recombinant proteins IFNα-GP5-Fc and IFNα-M-Fc were expressed by HEK293T eukaryotic expression system. The two recombinant proteins were mixed with ISA206VG adjuvant to immunize weaned piglets. The humoral immunity level was evaluated by ELISA and neutralization test, and the cellular immunity level was detected by ELISPOT test. The results showed that the NADC30-like lineage was the main epidemic lineage in China in recent years, and the combination of IFNα-GP5-Fc and IFNα-M-Fc could induce high levels of antibody and cellular immunity in piglets. This study may facilitate the preparation of a safer and more effective new PRRSV subunit vaccine.
Humans ; Animals ; Swine ; Porcine respiratory and reproductive syndrome virus/genetics* ; Porcine Reproductive and Respiratory Syndrome/prevention & control* ; HEK293 Cells ; Viral Envelope Proteins/genetics* ; Antibodies, Viral ; Viral Vaccines/genetics* ; Recombinant Proteins ; Vaccines, Subunit

Objective:To construct a self-examination index system for hospital legal practice, and provide effective reference for the self-examination work of hospital practice in accordance with the law.Methods:From May 2021 to September 2022, a multi-dimensional and multi-level indicator system was initially constructed through literature review and expert interviews; Delphi expert consultation method was used to carry out a three-round questionnaire survey, experts were invited to assess the importance of indicators, and the weight values of indicators were processed by using analytic hierarchy process-fuzzy comprehensive evaluation method.Results:The Cs value of consulting experts′ familiarity with the survey content was 0.84, Ca value of judgment basis was 0.78, Cr value of authoritative evaluation was 0.81, and Kendall W value was 0.630. The index system of hospital self-examination included 5 first-level indexes, 19 second-level indexes, and 30 third-level indicators. The 5 first-level indicators included institutional practice, personnel practice, disinfection and prevention of infectious disease, online diagnosis and treatment, and anti-fraud insurance, with weights of 0.235, 0.186, 0.188, 0.185, and 0.206 respectively. Among the second-level indicators, the weights of rational use of medical insurance fund, internet hospital and internet diagnosis and treatment, organization qualification and practice behavior were the highest, with values of 0.206, 0.185, 0.122 and 0.113 respectively. Among the third-level indicators, the internet hospital physician qualification, whether the hospital had obtained the license to practice, cracking down on fraudulent insurance practices, real-name medical treatment, and reasonable and standardized use of health insurance costs had the highest weight, which were 0.185, 0.122, 0.076, 0.065, and 0.065, respectively. Conclusions:The self-examination index system of medical institutions is scientific, which could help the medical institutions to practice self-examination and ensure medical quality and safety.

Objective To investigate the hemodynamic,cerebral perfusion and neurological function changes between unilateral symptomatic internal carotid artery occlusion(SICAO)and symptomatic middle cerebral artery occlusion(SMCAO)after superfical temporal artery-middle cerebral artery(STA-MCA)bypass surgery as well as the correlation between relative peak volume of blood flow(rPVOL)in STA measured by carotid Doppler ultrasonography(CDU)and relative cerebral blood flow(rCBF)by CT perfusion(CTP).Methods Retrospective analysis of 112 patients who diagnosed with unilateral SICAO or SMCAO through DSA and/or CT angiography(CTA)and underwent superficial temporal artery-middle cerebral artery(STA-MCA)bypass in the Department of Neurosurgery at First Affiliated Hospital of Soochow University from March 2019 to June 2022.The patients were divided into SICAO group(50 cases)and SMCAO group(62 cases)and followed up for 360 days.General clinical and imaging data of patients in two groups were collected.General clinical information included age,gender,clinical manifestations(stroke,transient ischemic attack[TIA]),hypertension,diabetes,smoking history,blood biochemical indicators(total cholesterol,triacylglycerol,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,high-sensitivity C-reactive protein),National Institute of Health stroke scale(NIHSS)scores at admission and 7 days after surgery,and modified Rankin Scale(mRS)scores at admission and 7,180 and 360 days after surgery(mRS scores 2 as good prognosis,＞2 as poor prognosis).Imaging data included hemodynamic parameters(STA diameter[D],resistance index[RI],time-averaged-mean velocity[TAMV],and time-average-peak flow velocity[TAPV])evaluated by CDU within 7 days before and 7,30,180 and 360 days after STA-MCA bypass,as well as CTP parameters(rCBF,relative cerebral blood volume[rCBV],relative mean transit time[rMTT]and relative time to peak[rTTP])of the head region of interest(ROI)before and 7,180 and 360 days after surgery.Patients were observed 1 year after surgery through outpatient or telephone follow-up to determine if they have experienced recurrent stroke(TIA,cerebral infarction,etc.)and other postoperative complications(subdural hematoma,cerebral hemorrhage,etc.).DSA imaging was also performed to determine the patency of vascular anastomosis of patients in SICAO and SMCAO groups.STA hemodynamic parameters,head CTP parameters,NIHSS scores,and mRS scores at different time points before and after STA-MCA bypass surgery were compared between SICAO and SMCAO groups correspondingly;STA hemodynamic parameters,head CTP parameters,and mRS scores were pairwise compared between different time points within each group.A correlation analysis was conducted between rCBF and rPVOL in STA which was measured by CTP and CDU accordingly in the SICAO and SMCAO groups to further determine the consistency of the blood flow through STA and intracranial cerebral blood flow.Results(1)There was no statistically significant difference in general clinical data between the two groups(all P＞0.05).(2)Comparison of STA hemodynamic parameters:D,TAMV,and TAPV of both groups significantly increased at 7,30,180,and 360 days after surgery(all P＜0.05)compared with preoperative,and reaching their peak at 7 days after surgery,and there was no statistically significant difference in D,TAMV,and TAPV among 30,180,and 360days after surgery(all P＞0.05).There was no statistically significant difference in D,TAMV,or TAPV between the two groups at each time point(D:F=2.286,TAMV:F=0.180,TAPV:Wald x=1.709;all P＞0.05).RI of the two groups was significantly reduced at 7,30,180,and 360 days after surgery(all P＜0.05)compared with preoperative,and there was no statistically difference in RI among 7,30,180,and 360 days after surgery(all P＞0.05).There was also no statistically difference in RI between the two groups at each time point(Wald x2=0.788,P＞0.05).(3)Comparison of CTP parameters between two groups:compared to preoperative,rCBF and rCBV in the SICAO group and SMCAO group increased at 7,180,and 360 days after surgery(all P＜0.05),there was no statistically difference in CTP parameters within the two groups at different time points(Wald x2 was 0.177,2.954,respectively,all P＞0.05),and the rMTT and rTTP of both groups decreased at 7,180,and 360 days after surgery(all P＜0.05),there was no significant difference in rMTT and rTTP between the two groups at different time points(Waldx2 was 2.157,1.706,respectively,all P＞0.05),and there was no statistically difference in the parameters of each postoperative time point within each group(all P＞0.05).(4)Comparison of vascular patency between two groups:1 year DSA showed that 91.1％(102/112)of patients were patent,with 92.0％(46/50)in the SICAO group and 90.3％(56/62)in the SMCAO group.There was no statistically difference between the two groups(x2=0.001,P＞0.05).The STA hemodynamics and intracranial CTP parameters of the two groups of patients with patent anastomosis were significantly improved compared to preoperative.A total of 10 patients were non-patent by 1 year DSA,including 4 cases in the SICAO group and 6 cases in the SMCAO group.In 1 non-patent SICAO patient and 3 non-patent SMCAO patients,the STA hemodynamic parameters evaluated by CDU 180 days and 360 days after surgery also showed corresponding improvement compared to preoperative,with an increase in TAMV and TAPV,and a decrease in RI.(5)Comparison of neurological improvement between the two groups:compared with preoperative,the mRS scores of the SICAO group and the SMCAO group significantly decreased at 7,180,and 360days postoperatively(all P＜0.05);there was no statistically difference in the mRS scores within each group at 7,180,and 360 days after surgery(P＞0.05).There was no statistically difference in mRS scores between the two groups at different time points including admission and 7,180 and 360 days after surgery(Wald x2=0.006,P＞0.05).The NIHSS scores of the SICAO group and the SMCAO group decreased at 7 days after surgery compared to admission(Z was 21.040,-5.183,respectively,all P＜0.01),and there was no statistically difference in NIHSS scores between the two groups at admission and 7 days after surgery(both P＞0.05).(6)Spearman rank correlation analysis showed that rPVOL and rCBF were highly positively correlated in the SICAO group(r=0.865,P＜0.01)and in the SMCAO group(r=0.864,P＜0.01).Conclusions Unilateral STA-MCA bypass can improve cerebral perfusion and neurological function in patients with SICAO and SMCAO,and there is no statistical difference between the two groups of patients.The rPVOL measured by CDU was highly correlated with the rCBF in patients after STA-MCA bypass surgery.