Perinatal cerebral white matter injury is the most common form of brain injury in premature infants which can lead to developmental disorders of the neurological system,even long-term neurological sequala.The pathogenesis of white matter injury is complicated,and until now there is no effective intervention option.In recent years,as the structural and functional integer of the nervous system,neurovascular unit has attracted much attention in the neuroscience field.The constituents of neurovascular unit and their interaction in the white matter,as well as the progress in the pathophysiology,prevention and treatment of white matter injury are reviewed in this paper.

ObjectiveTo investigate the role of active protein C (APC) in lipopolysaccharide (LPS) induced microglia activation.MethodsMicroglia from one day old Sprague-Dawley newborn rat was collected, purified and identified by primary culture and immunofluorescence staining, and then was randomly divided into four groups including LPS group (1.0μg/ml LPS plus 10μl phosphate buffered saline 12 h later), LPS+ APC group (1.0μg/ml LPS plus 0.1μg/ml APC 12 h later), APC group (10μl phosphate buffered saline plus 0.1μg/ml APC 12 h later) and control group (10μl phosphate buffered saline at each time point). The morphology of micaroglia in all groups was observed under microscope, and the expression of tumor necrosis factor-α (TNF-α) and protease-activated receptor-1 (PAR-1) were determined by immunofluorescence staining. One-way analysis of variance and LSD test were applied for statistical analysis.ResultsPrimary culture microglia was successful and the purity was no less than 99%. In LPS group, the microglia morphology was activated, and the expression of TNF-α was increased significantly than the control group (2.11±0.35 vs 1.38±0.28, LSD test,P=0.002). In LPS+APC group, the microglia morphological change was reversed, and the expression of TNF-α had no significant difference with the control group (1.35±0.36 vs 1.38±0.28, LSD test,P>0.05). The expression of PAR-1 in LPS+APC group was higher comparing with that in the control group (4.60±0.84 vs 2.64±0.41, LSD test,P=0.008) and the LPS group (2.44±0.86, LSD test,P=0.002). The expression of PAR-1 in APC group and LPS group had no obvious difference with control group (2.62±0.69, 2.44±0.86 vs 2.64±0.41, LSD test, bothP>0.05).ConclusionsBy increasing the level of PAR-1 in microglia, active protein C could inhibit the activation of miciroglia and the expression of TNF-α induced by lipopolysaccharide, therefore, protecting the brain tissues from inflammation-induced damage.

Objective To explore the febrile response and placental pathological inflammation of pregnant rats exposed to intrauterine infection in late gestation.Methods Pregnant Sprague-Dawley rats at gestational day 18 were randomly divided into control group and intrauterine-infected group with six rats in each.The intrauterine-infected group was intraperitoneally injected with 350 μ g/kg lipopolysaccharide to establish a rat model of intrauterine infection,while the control group was injected with sterile saline of the same dose.Core temperature was measured every 1 h after intraperitoneal injection of lipopolysaccharide or saline for 8 h.At gestational day 19,after anesthesia,the placentas were taken and stained with HE.The expression levels of tumor necrosis factor-α,interleukin-6,and interleukin-1β in the placenta were determined by enzyme linked immunosorbent assay.Student t test was used for statistical analysis.Results (1) There was no temperature difference between the two groups before experimental treatment (P ＞ 0.05).Core temperature was increased 1 h after the lipopolysaccharide injection,reaching (37.67 ±0.08) ℃.The increase of temperature was significant compared with the control group [(37.13 ± 0.08) ℃,t=10.178,P ＜ 0.01].Fever was lowered 2 h later and the rats became hypothermic with body temperature below 37 ℃ in the intrauterine-infected group.The body temperature in the intrauterine-infected group after 2-6 h was (37.70 ± 0.10),(37.23 ± 0.05),(36.57 ± 0.06),(36.60 ± 0.10) and (36.57 ± 0.08) ℃,respectively,compared with the control group [(36.83 ±0.12),(36.63 ± 0.12),(36.71 ± 0.07),(36.87±0.12),and (36.77±0.08) ℃,respectively],the differences being all statistically significant (t=11.402,11.163,-4.025,-4.000 and-4.243,all P ＜ 0.01).(2) HE staining revealed large amounts of neutrophils infiltration,vascular enlargement and congestion in the placenta of the intrauterine-infected rats.No inflammatory cell infiltration was observed in the control placentas.(3) The expression levels of proinflammatory cytokine tumor necrosis factor-α [(0.62 ± 0.02) ng/g],interleukin-6 [(66.12 ± 5.11) ng/g],and interleukin-1β [(7.09± 1.23) ng/g] in the intrauterine-infected group were higher than those in the control group [(0.27±0.01),(16.71 ±1.55) and (2.86 ± 0.38) ng/g,respectively].The differences were all statistically significant (t=-26.608,-18.749 and-5.714,all P ＜ 0.01).Conclusion After exposure to lipopolysaccharide in late gestation,pregnant rats show significant inflammatory response in the placenta,with suppression of febrile response and presence of hypothermia.

Objective To explore the clinical phenotypes and the genetic cause for a boy with unexplained growth retardation,nephrocalcinosis,auditory anomalies and multi-organ/system developmental disorders.Method Routine G-banding and chromosome microarray analysis were applied to a child with unexplained growth retardation,nephrocalcinosis,auditory anomalies and multi-organ/system developmental disorders treated in the Department of Pediatrics of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology in September 2015 and his parents to conduct the chromosomal karyotype analysis and the whole genome scanning.Deleted genes were searched in the Decipher and NCBI databases,and their relationships with the clinical phenotypes were analyzed.Result A six-month-old boy was refered to us because of unexplained growth retardation and feeding intolerance.The affected child presented with abnormal manifestation such as special face,umbilical hernia,growth retardation,hypothyroidism,congenital heart disease,right ear sensorineural deafness,hypercalcemia and nephrocalcinosis.The child's karyotype was 46,XY,16qh+,and his parents' karyotypes were normal.Chromosome microarray analysis revealed a 1 436 kb deletion on the 7q1 1.23 (72701098_74136633) region of the child.This region included 23 protein-coding genes,which were reported to be corresponding to Williams-Beuren syndrome and its certain clinical phenotypes.His parents' results of chromosome microarray analysis were normal.Conclusion A boy with characteristic manifestation of Williams-Beuren syndrome and rare nephrocalcinosis was diagnosed using chromosome microarray analysis.The deletion on the 7q1 1.23 might be related to the clinical phenotypes of Williams-Beuren syndrome,yet further studies are needed.

Central precocious puberty (CPP) is a common pediatric endocrine disease caused by premature activation of the hypothalamic-pituitary-gonadal axis, featured by rapid development of internal and external reproductive organs and secondary sexual characteristics in girls before age 8 and boys before age 9.The gonadotropin-releasing hormone analogue (GnRHa) is the first choice for the treatment of CPP.Currently, 3.75 mg/ month sustained -release short-acting dosage form (1M depot formulations) is the most commonly used in China.The development of long-acting dosage form will reduce injection times and clinic visits.At present, the 3-month long-acting dosage form (11.25 mg 3M depot formulations) of Leprorelin microsphere has been approved in China.However, clinical practice experience of 3-month Leuprorelin acetate depot formulations is lacking in China.Therefore, in this paper, existing clinical evidence for this dosage form was reviewed to provide evidence-based medicine support for its clinical application.

Objective:To investigate the antibiotics resistance of patients with Helicobacter pylori ( H. pylori) infection of different age in Ningxia. Methods:From July to December 2021, a total of 1 040 patients with H. pylori infection confirmed by 14C-urea breath test who had no history of H. pylori treatment and underwent gastroscopy were selected from the H. pylori special outpatient clinics from Ningxia Hui Autonomous Region People′s Hospital, Ningxia Hospital of Integrated Traditional Chinese and Western Medicine, Yuanzhou District People′s Hospital of Guyuan, Wuzhong People′s Hospital, the Second People′s Hospital of Shizuishan, People′s Hospital of Zhongwei, Yinchuan First People′s Hospital. Gastric mucosa specimens were obtained under gastroscopy and cultured for H. pylori in vitro. Harvested H. pylori were detected for H. pylori drug resistance phenotype. Kirby-Bauer disk diffusion method was used to detect antibiotic sensitivity. Previous use of antibiotics of patients were recorded. The characteristics of primary drug resistance of people≤44, 45 to 59, and ≥60 years old were analyzed. Chi-square test was used for statistical analysis. Results:A total of 538 H. pylori strains were obtained from 1 040 gastric mucosa specimens cultured in vitro, with a positive rate of 51.7%. A total of 187 patients could provide information on history of antibiotics usage. The primary drug resistance rates of metronidazole, clarithromycin and levofloxacin were high, which were 95.5% (514/538), 44.6% (240/538) and 45.4% (244/538), respectively; however drug resistance of amoxicillin, furazolidone and tetracycline were not found. The double drug resistance rate was 36.4% (196/538), mainly resistant to metronidazole and clarithromycin or metronidazole and levofloxacin, the drug resistance rates were 17.8% (96/538), 18.2% (98/538), respecitively. The triple drug resistance rate was 25.5% (137/538), all of the strains were metronidazole, clarithromycin and levofloxacin resistant strains. The primary drug resistance rates to levofloxacin and clarithromycin in patients with H. pylori infection who had previous history of quinolones and macrolides were 60.9% (28/46) and 63.4% (83/131), respectively; which were higher than those of patients who had not used corresponding drugs (41.8%, 59/141 and 39.3%, 22/56), and the differences were statistically significant ( χ2=5.05 and 9.23, P=0.023, 0.002). The drug resistance rates of metronidazole of ≤44, 45 to 59, and ≥60 years old group were 94.2% (163/173), 95.5% (231/242) and 97.6% (120/123), respectively, and the differences were not significant ( P>0.05). The single drug resistance rates of levofloxacin of ≤44, 45 to 59, and ≥60 years old group were 34.7% (60/173), 48.3% (117/242) and 54.5% (67/123), respectively, and the differences were statistically significant ( χ2=12.95, P=0.002). The levofloxacin resistance rate of ≤44 years old group was lower than that of 45 to 59, and ≥60 years old group, and the differences were statistically significant ( χ2=7.70 and 11.49, P=0.006, 0.001). The single drug resistance rates of clarithromycin of ≤44, 45 to 59, and ≥60 years old group were 36.4% (63/173), 50.4% (122/242) and 44.7% (55/123), respectively, and the differences were statistically significant ( χ2=8.00, P=0.018). The clarithromycin resistance rate of ≤44 years old group was lower than 45 to 59 years old group, and the difference was statistically significant ( χ2=8.00, P=0.005). Dual drug resistance rates of levofloxacin and clarithromycin of ≤44, 45 to 59 and ≥60 years old group were 49.7%(86/173), 70.2%(170/242), 45.5%(56/123), and the difference was statistically significant( χ2=27.63, P<0.001). The resistance rate of clarithromycin and levofloxacin in 45 to 59 years old group was higher than that in ≤44 and ≥60 years old group, and the difference was statistically significant ( χ2=18.00 and 21.13, both P<0.001). Conclusions:Primary drug resistance rates to metronidazole, levofloxacin and clarithromycin are high in patients with H. pylori infection of different ages in Ningxia. Individualized eradication therapy guided by drug resistance test is recommended.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.