Dynamic evolution of brain structural patterns in liver transplantation recipients: a longitudinal study based on 3D convolutional neuronal network model.

OBJECTIVES: To evaluate the dynamic evolution process of overall brain health in liver transplantation (LT) recipients, we employed a deep learning-based neuroanatomic biomarker to measure longitudinal changes of brain structural patterns before and 1, 3, and 6 months after surgery. METHODS: Because of the ability to capture patterns across all voxels from a brain scan, the brain age prediction method was adopted. We constructed a 3D-CNN model through T1-weighted MRI of 3609 healthy individuals from 8 public datasets and further applied it to a local dataset of 60 LT recipients and 134 controls. The predicted age difference (PAD) was calculated to estimate brain changes before and after LT, and the network occlusion sensitivity analysis was used to determine the importance of each network in age prediction. RESULTS: The PAD of patients with cirrhosis increased markedly at baseline (+ 5.74 years) and continued to increase within one month after LT (+ 9.18 years). After that, the brain age began to decrease gradually, but it was still higher than the chronological age. The PAD values of the OHE subgroup were higher than those of the no-OHE, and the discrepancy was more obvious at 1-month post-LT. High-level cognition-related networks were more important in predicting the brain age of patients with cirrhosis at baseline, while the importance of primary sensory networks increased temporarily within 6-month post-LT. CONCLUSIONS: The brain structural patterns of LT recipients showed inverted U-shaped dynamic change in the early stage after transplantation, and the change in primary sensory networks may be the main contributor. KEY POINTS: • The recipients' brain structural pattern showed an inverted U-shaped dynamic change after LT. • The patients' brain aging aggravated within 1 month after surgery, and the subset of patients with a history of OHE was particularly affected. • The change of primary sensory networks is the main contributor to the change in brain structural patterns.

[Textual research on illustration of Heshouwu in historical Bencao literature and its system of assessing quality by distinguishing features of traditional Chinese medicinal materials].

As a medicine, Heshouwu was first appeared in Kaibao Bencao in Song Dynasty, which was a traditional tonic medicine. In recent years, the hepatotoxicity of Heshouwu has attracted great attention of domestic and foreign scholars. This paper has carried out textual research on illustration, quality evaluation, toxic and side effects of the Heshouwu in the historical Bencao(materia medica) literature. Illustrations of Heshouwu in the historical Bencao literatures are basically Polygonum multiflorum. Only in Taiyixian Zhibencao Yaoxing Daquan and Tujie Bencao, illustrations of Heshouwu may be Pteroxygonum giraldii and Dioscorea bulbifera, respectively. Illustrations of Heshouwu in the historical Bencao literatures are quite different from those of the genus Cynanchum in Asclepiadaceae. In the biography of Heshouwu, the author has noticed the abnormal vascular bundle in the root tuber of Heshouwu, which was inherited by the historical Bencao literatures. This is also one of the evidences to infer that Heshouwu is from Polygonaceae plant P. multiflorum. The description of abnormal vascular bundle in the historical Bencao literatures has been developed and evolved into the term "brocaded patterns", and it is considered that "five petals are good". Furthermore, ancient medical scientists have noticed that there are toxic differences in different characters of Heshouwu, that is, "Heshouwu with abundant parenchyma cells, low fibrous and large is superior in quality", "the hard and fibrous root tuber of P. multiflorum has toxic side effects". In this paper, the germplasm and the theory of assessing the quality by distinguishing features of traditional Chinese medicinal materials of Heshouwu in the historical Bencao literatures are reviewed, which provides the basis of materia medica for the quality evaluation of Heshowu.

[Extracting Paeonia lactiflora planted area in Dangshan of Anhui province based on ZY-3 remote sensing image].

In order to comprehensively monitor the dynamic change of Paeonia lactiflora planting area,the investigation of P. lactiflora planting area in Dangshan was carried out. It can provide reference for the planting detection of P. lactiflora in Huaibei Plain.Based on remote sensing technology,this paper extracts the planting area of P. lactiflora in Dangshan in 2018 by using the minimum distance method,maximum likelihood method,parallel hexahedron method and Mahalanobis distance method,using the remote sensing image of ZY-3 Satellite as the data source,and makes a comparative analysis with the results. The results show that the maximum likelihood method is better than the other three methods. This method can provide reference for remote sensing monitoring of P. lactiflora planting area in China.

[Planting area estimation of Paeonia ostii based on RS--by case study in Dangshan of Anhui province].

Moutan Cortex is one kind of famous medicinal materials. The dry root bark of Paeonia ostii which is a genuine medicinal material produced in Tongling,Anhui province,and later was introduced to Heze,Shandong province and Bozhou,Anhui province.Dangshan county is located at the northern end of Anhui province and adjacent to Shandong province. Its medicinal seedlings were came from Heze,Shandong province. At present,there is a lack of scientific investigation on the planting area of P. ostii in north China plain. On the basis of field investigation and remote sensing technology,through the data source provided by the remote sensing image of " Resources 3"( ZY-3),combined with the biological characteristics of P. ostii,the planting area of P. ostii in Dangshan county was extracted by field investigation and supervisory classification. The supervise classification method with the highest interpretation accuracy so far,the overall accuracy was 97. 81%,Kappa coefficient 0. 96. The results showed that the remote sensing classification method based on the maximum likelihood classification could extract P. ostii plots in the study area effectively. This study provides a scientific basis for the protection and rational utilization of traditional Chinese medicine resources,the development policy of traditional Chinese medicine industry and the long-term development plan in Dangshan county,and provides technical support for the poverty alleviation of traditional Chinese medicine industry in Dangshan county. It provides scientific reference for the application of remote sensing technology to investigate the planting area of P. ostii in in north China plain.

[Study on TLC identification and UPLC determination method of atractylenolide in Atractylodes macrocephala].

This research is to establish TLC and UPLC methods for simultaneous determination of 3 atractylenolides in Atractylodes macrocephala. Silica gel GF254 plate was used for identification of A. macrocephala, and UPLC-PDA gradient elution method was used to simultaneously determine atractylenolide Ⅰ, Ⅱ and Ⅲ. The Waters BEH C18 column（2.1 mm×100 mm,1.7 µm）with acetonitrile-water as mobile phase and the wavelength of UV detector of 235 nm were performed. The quality control study showed that the characteristic for identification by TLC was distinct and highly specific. The method of content determination was in accordance with the regulations. The quantitative evaluation of atractylenolide Ⅰ,Ⅱ and Ⅲ was in good linear range（r>0.999 9）, and the average recovery was 93.48%（RSD 1.4%）,94.97%（RSD 1.6%）,92.71%（RSD 1.2%）,respectively. TLC identification was in good specificity and repeatability, and the UPLC-PDA method for the simultaneous determination of 3 atractylenolides was simple and reliable for the quality control of A.macrocephala.

[Research on evolution and transition of quality evaluation of Shihu].

Shihu is one of the most valuable Chinese medicines in China. The sources of Shihu are complex and the quality evaluation of it mainly depends on morphologic characteristics distinction. In order to understand the Shihu's quality evaluation concept of Chinese herbalists in the past dynasties. This paper summarizes the methods of quality evaluation in ancient bencao systematically. The ancient bencao records that the quality of Shihu is closely related to its germplasm, habitat, processing and character. The concept of germplasm about shihu includes generalized and narrow sense, besides, the clinical applications of Dendrobium huoshanenese, D. officinale and D. nobile are focused on different diseases. D. huoshanenese has been regarded as Dao-di herbs since Qing Dynasty. The main products of Shihu contain fresh goods and dry goods, their clinical applications are also treated differently. Fengdou is one of the commodity specifications in Shihu. Its processing method probably dated from the Qing Dynasty, but now, it has become the mainstream commodityform. There was a common sense that different kinds of Shihu owed different characters and curative effects in ancient bencao, and the quality would enhance with the increasing viscidity. Therefore, the "Germplasm", "Geoherbs", "processing", "characters" were integrated into traditional quality evaluation methods of Shihu. Meanwhile, we should pay attention to the clinical efficacy of shihu with different species and processing methods.

[Microscopic anatomy of abnormal structure in root tuber of Pueraria lobata].

Puerariae Lobatae Radix, also known as Gegen, is a root derived from Pueraria lobata. Based on field investigation and the developmental anatomy of root tuber, we have elucidated the relationship between the growth of root tuber and the anomalous structure. The results of analysis showed that the root system of P. lobata was developed from seed and adventitious root and there existed root tuber, adventitious root and conductive root according to morphology and function. The root tuber was developed from adventitious root, its secondary structure conformed to the secondary structure of dicotyledon's root. With the development of root, the secondary phloem of root tuber appeared abnormal vascular tissue, which was distributed like ring in the outside of secondary vascular tissue. The root tuber might have 4-6 concentric circular permutation abnormal vascular tissuelobate, and was formed by the internal development of abnormal vascular tissue. The xylem and phloem of abnormal vascular tissue were the main body of the root tuber. The results reveal the abnormal anatomical structure development of P. lobata, also provides the theoretical basis for reasonable harvest medicinal parts and promoting sustainable utilization of resources of P. lobata.

[Effect of Yunnan herb Laggera pterodonta against influenza A (H1N1) virus in vitro].

Laggera pterodonta is commonly used for treating influenza in Southwest China, especially in Yunnnan province. The main clinical effects of L. pterodonta include anti-influenza, anti-microbial, anti-inflammatory. To investigate the anti-influenza A (H1N1) virus effect of L. pterodonta, neutralization inhibition and proliferation inhibition tests were performed. MDCK culture method was used to observe the cytopathic effect (CPE) of extracts from L. pterodonta in inhibiting influenza A (H1N1) virus and haemagglutination titre of H1N1 virus in vitro. The culture medium were collected at 24 h, 48 h, 72 h, 96 h, and detected by Real time RT-PCR, in order to compare the effect of different extracts from L. pterodonta on in vitro proliferation of H1N1, virus. The result of neutralization inhibition test showed that hemagglutination titer of ethyl acetate extract were 8 times lower at 72 h; in proliferation inhibition test, hemagglutination titer of ethyl acetate extracts reduced by 2 and 4 times. According to the results of Real time RT-PCR test, the H1N1 inhibition ratio of ethyl acetate extract was 72.5%, while the proliferation inhibition ratio of ethyl acetate extract was 25.3%; as for petroleum ether extracts, the H1N1 inhibition ratio was 60.2%, while the proliferation inhibition ratio was 81.4%. In conclusion, both ethyl acetate extract and petroleum ether extract of L. pterodonta have significant neutralization and direct proliferation inhibition effects on influenza A virus.

Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease: Two case reports and a review of the literature.

BACKGROUND: Central nervous system graft-vs-host disease (CNS-GVHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation. Currently, establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out. CASE SUMMARY: Here, we present two patients with CNS-GVHD. Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes, and had abnormal cerebrospinal fluid (CSF) studies as determined by CSF and blood immune biomarker examinations, suggestive of suspected CNS-GVHD. Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients, we did not attempt to perform a brain biopsy, but prompted the initiation of empirical immunosuppressive therapy. In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings, a final diagnosis of CNS-GVHD was made. CONCLUSION: CSF and blood immune biomarker examinations facilitated the diagnosis of CNS-GVHD, which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

[Adaptability and purification of dengue-III virus D9964 strain in KMB17 cells and proliferation kinetics of adapted strain].

To select the adaptive strain of Dengue-III virus D9964 strain (China strain) in KMB17 cells, elucidate the biological characteristics and proliferation kinetics of adapted strain,and to lay the foundation for the development dengue inactivated vaccine and attenuated live vaccine. Dengue-III virus D9964 strain was firstly identified by amplification of the type-specific gene segment of dengue virus by RT-PCR, and the titer was determined. The virus was then subcultured in KMB17 cells with 4.0 MOI till completely adaptive to multiply in cell S. After subculturing in KMB17 cells for 10 consecutive passages, the adapted strain was screened, and purified through plaque. Virus titer of each passage was measured by microtitrimetry, and the antigenicity was detected by IFA. The purified virus RNA extraction of 3-8 day cultured from KMB17 cells, was performed to detect the proliferation kinetics of adapted strain. The results showed that after continuous subculture, dengue-III virus D9964 (China) strain could stably proliferate in KMB17 cells, a highly puried virus adapted strain was obtained through plaque purification. Purified strain maintained the good antigenicity with a highest replicating activity during the 5th-6th day.

[The analysis of human papillomavirus type 16 E6/E7 genetic variability in Yunnan Province, China].

To investigate E6 and E7 gene variations of human papillomavirus type 16 in Yunnan Province, DNA was extracted from 2000 gynecological outpatient samples. For Human papillomavirus (HPV) genotyping, the genomic DNA was first amplified by the consensus MY09/MY11 primer pair followed by nested PCR with GP5+/GP6+ primers, then the PCR products were subjected to direct DNA sequencing. A total of 20 HPV-16 viral DNAs were identified. E6 and E7 genes of HPV-16 viral DNA were then amplified using E6 and E7 specific primers, the PCR products were purified and sequenced. The results showed that mutations were found at nucleotide position 178 of HPV-16 E6 gene in 10 cases,the mutation rate was 50%; For HPV-16 E7 gene, the mutations were found at nucleotide position 647 in 10 cases; the mutation rate was 50%. Phylogenetic analysis showed that Asian (As) variants of HPV-16 were predominated in Yunnan, China. None of African-1, African-2 variants of HPV-16 was found in this region.