Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis

Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and the lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal LSEC activation not only changes their own physicochemical properties but also interrupts their communication with hepatic stellate cells and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and aggravation of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.

Effect of Combined Frequency Stimulation on The Electrophysiology of Granule Neurons in The Hippocampal Dentate Gyrus Area of Hindlimb Unloading Mice / 生物化学与生物物理进展

ObjectiveIn recent years, the negative impact of microgravity on astronauts’ nervous systems has received widespread attention. The repetitive transcranial magnetic stimulation (rTMS) technology has shown significant positive effects in the treatment of neurological and psychiatric disorders. The potential benefits of combined frequency stimulation (CFS) which combines different frequency stimulation patterns in ameliorating neurological dysfunctions induced by the microgravity environment, still require in-depth investigation. Exploring the therapeutic effects and electrophysiological mechanisms of CFS in improving various neurological disorders caused by microgravity holds significant importance for neuroscience and the clinical application of magnetic stimulation. MethodsThis study employed 40 C57BL/6 mice, randomly divided into 5 groups: sham group, hindlimb unloading (HU) group, 10 Hz group, 20 Hz group, and combined frequency stimulation (10 Hz+20 Hz, CFS) group. Mice in all groups except the sham group received 14 d of simulated microgravity conditions along with 14 d of repetitive transcranial magnetic stimulation. The effects of CFS on negative emotions and spatial cognitive abilities were assessed through sucrose preference tests and water maze experiments. Finally, patch-clamp techniques were used to record action potentials, resting membrane potentials, and ion channel dynamics of granule neurons in the hippocampal dentate gyrus (DG) region. ResultsCompared to the single-frequency stimulation group, behavioral results indicated that the combined frequency stimulation (10 Hz+20 Hz) significantly improved cognitive impairments and negative emotions in simulated microgravity mice. Electrophysiological experiments revealed a decrease in excitability of granule neurons in the hippocampal DG region after HU manipulation, whereas the combined frequency stimulation notably enhanced neuronal excitability and improved the dynamic characteristics of voltage-gated Na+ and K+ channels. ConclusionThe repetitive transcranial magnetic stimulation with combined frequencies (10 Hz+20 Hz) effectively ameliorates cognitive impairments and negative emotions in simulated microgravity mice. This improvement is likely attributed to the influence of combined frequency stimulation on neuronal excitability and the dynamic characteristics of Na+ and K+ channels. Consequently, this study holds the promise to provide a theoretical basis for alleviating cognitive and emotional disorders induced by microgravity environments.

Phase Separation of Biomacromolecules and Its Important Role in Transcriptional Regulation / 生物化学与生物物理进展

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

The Genetic Polymorphism and Structural Analysis of 47 Microhaplotypes in a Jiangsu Changshu Chinese Han Population / 生物化学与生物物理进展

ObjectiveTo investigate the genetic polymorphism and structure of 47 autosomal microhaplotypes in the Han population in Changshu City, Jiangsu Province, and to evaluate the forensic efficiencies and forensic parameters. MethodsThe DNA library of unrelated individual samples was prepared according to MHSeqTyper47 kit manual and sequenced on the MiSeq FGx platform. Microhaplotype genotyping and sequencing depth statistics were processed using MHTyper. The genetic information of samples was then evaluated. The fixation index and genetic distance between the Jiangsu Changshu population and the reference populations in the 1000 Genomes Project phase 3 (1KG) were calculated, and forensic parameters were evaluated. ResultsThe fixation index and genetic distance between the Han population in Changshu, Jiangsu, and the CHB (Han Chinese in Beijing, China) reference population in 1KG were the lowest. The effective allele number (Ae) of each locus is also the closest between the two populations. The combined matching probability (CMP) of the Changshu Han population is close to the 5 populations of the East Asian reference super-population in 1KG, which is 1.25×10-36, and the combined probability of exclusion reached 0.999 999 999 964 1. ConclusionThis study reported the genetic polymorphism and allele frequency of 47 microhaplotypes in a Han population in Changshu City, Jiangsu Province. This information provides a data basis for 47 microhaplotypes in forensic applications. In addition, the polymorphism differences between the 1KG reference population and the Han population in Changshu, Jiangsu were compared, and the genetic structure of 47 microhaplotypes in the Han population in Changshu, Jiangsu was revealed. In general, the reference data of the East Asian super-population in 1KG is more in line with the genetic characteristics of Han population in Changshu, Jiangsu.

The nursing intervention of ultrasound drug penetration in the application of the digestive tract cancer patients′ postoperative rapid recovery / 中国实用护理杂志

Objective:To explore the impact of nursing intervention in strengthening the implementation of ultrasound drug penetration therapy on postoperative rapid recovery of patients with digestive tract tumors after surgery, and to provide reference for the formulation of intervention plans for postoperative rapid recovery of digestive tract tumor patients.Methods:A randomized controlled trial was used. From April to July 2021, 120 postoperative patients with digestive tract tumors admitted to the Second Affiliated Hospital of Dalian Medical University were selected and divided into a control group, a dispersed treatment group, and a concentrated treatment group according to the random number table method, with 40 patients in each group. The control group mainly received routine accelerated rehabilitation surgical care, supplemented by early rehabilitation training; the dispersed treatment group received nursing intervention with ultrasound drug penetration therapy on the basis of the control group, once a day in the morning and once in the afternoon, lasting for 30 min each time; on the basis of the control group, the concentrated treatment group received nursing intervention of one-time concentrated ultrasound drug penetration therapy for 60 min. The gastrointestinal reactions, intestinal function recovery, hospitalization, postoperative complications, and nursing satisfaction of each group of patients were observed and compared using one-way ANOVA, LSD- t test, and χ2 test. Results:There were 27 males and 13 females in the control group, aged (61.85 ± 16.85) years old. while 23 males and 17 females in the dispersed treatment group aged (60.90 ± 16.88) years old, and 23 males and 17 females in the concentrated treatment group aged (59.80 ± 13.58) years old. The duration of postoperative nausea, vomiting, and abdominal distension symptoms, recovery time of bowel sounds, recovery time of exhaust, and first meal time in the dispersed treatment group and concentrated treatment group were (38.58 ± 2.74), (17.45 ± 1.92), (38.76 ± 3.34), (50.04 ± 2.57) h and (36.79 ± 2.58), (16.48 ± 1.85), (36.98 ± 2.28), (48.25 ± 3.07) h, respectively, which were lower than those in the control group (43.13 ± 3.56), (21.24 ± 2.50) (42.65 ± 3.78), (52.21 ± 3.15) h, the differences were statistically significant ( t values were 3.38-9.68, all P<0.05). The duration of postoperative nausea, vomiting, and abdominal distension symptoms, recovery time of bowel sounds, recovery time of exhaust, and first meal time in the concentrated treatment group were shorter than those in the dispersed treatment group, and the differences were statistically significant ( t values were 2.31-3.01, all P<0.05). The time to get out of bed activity and hospitalization of patients in the dispersed treatment group and the concentrated treatment group were (5.83 ± 1.20) h, (9.90 ± 2.12) d and (7.35 ± 2.13) h, (8.30 ± 1.42) d, respectively. The control group was (4.39 ± 1.53) h and (14.93 ± 2.56) d, respectively. The time to get out of bed activity and hospitalization of patients in the dispersed treatment group and the concentrated treatment group were better than those in the control group, while the time to get out of bed activity and hospitalization of patients in the concentrated treatment group were better than those in the dispersed treatment group, the differences were statistically significant ( t values were -7.14-14.34, all P<0.05). The incidence of intestinal obstruction was 15.0% (6/40) in the control group, 5.0% (2/40) in the dispersed treatment group, and 0 in the concentrated treatment group, with a statistically significant difference ( χ2=7.50, P<0.05). The nursing satisfaction of patients in the concentrated treatment group reached 100.00% (40/40), which was 92.5% (37/40) and 85.0% (34/40) in the dispersed treatment group and control group, with a statistically significant difference ( χ2=6.49, P<0.05). Conclusions:Nursing intervention through ultrasound drug penetration therapy, especially centralized treatment, can significantly improve postoperative intestinal function, reduce postoperative gastrointestinal reactions, shorten hospitalization time, reduce postoperative complications, accelerate patient recovery, and provide effective nursing intervention plans for clinical practice. It is worth promoting and applying.

Effects of Cochlear Implantation on Ipsilateral Tinnitus in Post-lingual Adault Recipients / 听力学及言语疾病杂志

Objective To study the changes of tinnitus after cochlear implantation in post-lingual adault recip-ients and analyze the factors that affect tinnitus.Methods A total of 47 postilingually-deafened adult subjects with tinnitus who underwent cochlear implantation at the Department of Otology,the first affiliated hospital of Zheng-zhou University,from January 2017 to December 2021.The subjects were evaluated using tinnitus handicap invento-ry(THI)and visual analogue scale(VAS)before cochlear implantation and 6 months after cochlear implant surger-y.Results Among 47 subjects who were eligible for this study,the THI scores were 36.94±13.337,14.48± 12.726,respectively,before CI and 6 months after cochlear implantation.The VAS scores were 5.13±1.676 be-fore and 2.34±1.903 after cochlear tmplantation.Statistical analysis showed significant differences in THI and VAS scores before and after cochlear implantation(P＜0.05).A total of 18 patients experienced complete tinnitus suppression,14 patients experienced alleviation of tinnitus,tinnitus remained unchanged in 13 patients,tinnitus worsened in 2 patients,and the overall efficiency was 66.0％(31/47).The tinnitus alleviation rate was signifant higher in the patients with tinnitus history of ≤5 years than the patients with tinnitus history of＞5 years(P＜0.05).There was a statistically significant difference in tinnitus alleviation between the patients with mild tinnitus and the patients with more than mild tinnitus before surgery(P＜0.001).Conclusion Cochlear implantation has an inhibitory effect on tinnitus in adults.Patients with shorter duration of the tinnitus and higher tinnitus handicap are more likely to experience tinnitus improvement after cochlear implantation.

Mechanisms of platelet-derived growth factor-BB regulation of hypoxia-inducible factor-1α expression in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国新生儿科杂志

Methods:A total of 160 Wistar neonatal rats were assigned into normoxia group, HPH group, normoxia+PDGF-BB group, HPH+PDGF-BB group and HPH+PDGF-BB inhibitor (STI571) group using random number table method (32 rats in each group), each group was further assigned into 4 subgroups on d3, d7, d14 and d21 (8 rats in each subgroup). HPH model was established using nitrogen-oxygen mixture with an oxygen concentration of 10%±0.5%. PDGF-BB groups were injected with adenovirus encoding PDGF-BB in the tail vein. HPH+STI571 group was given STI571 intragastrically. On d3, d7, d14 and d21 after modeling, mean right ventricular systolic pressure (RVSP) was examined. Morphological changes of small pulmonary arteries were observed using HE staining and indicators of pulmonary vascular remodeling calculated. Immunohistochemistry was used to determine the protein levels of PDGF-BB, HIF-1α and proliferation-associated protein nuclear protein Ki67 in the pulmonary vasculature of each group. RT-qPCR was used to determine the mRNA levels of PDGF-BB, HIF-1α and Ki67 in lung tissue.Results:At all time points, RVSP was higher in the HPH group than the normoxia group ( P<0.05), higher in the HPH+PDGF-BB group than the HPH group ( P<0.05), and lower in the HPH+STI571 group than both the HPH+PDGF-BB group and the HPH group ( P<0.05). On d3 after modeling, pulmonary vascular remodeling occurred in the HPH+PDGF-BB group; on d7, pulmonary vascular remodeling occurred in the PDGF-BB group and the HPH group. Pulmonary vascular remodeling appeared later and to a lesser extent in the HPH+STI571 group than the other hypoxic groups. On d3, d7 and d21 after modeling, protein and mRNA levels of PDGF-BB, HIF-1α and Ki67 in the HPH+PDGF-BB group were higher than the other groups ( P<0.05). The protein and mRNA expression levels of PDGF-BB, HIF-1α and Ki67 in the HPH+STI571 group were lower than the HPH+PDGF-BB group and the HPH group at all timepoints ( P<0.05). Conclusions:PDGF-BB up-regulates HIF-1α expression, participates in PASMC proliferation, exacerbates pulmonary vascular remodeling and increases pulmonary artery pressure in neonatal rats with HPH.Obiective:To study the roles of platelet-derived growth factor-BB (PDGF-BB) in hypoxic pulmonary hypertension (HPH) and the mechanisms of regulating hypoxia-inducible factor-1α (HIF-1α) expression, promoting the proliferation of pulmonary arterial smooth muscle cells (PASMC) and participating in the remodeling of pulmonary vessels.

Analytical sensors based on smartphones for real-time detection in forensic science:progress and application / 中国法医学杂志

In recent years,with the rapid development and widespread popularity of smartphones,analytical sensors based on different action principles have provided an effective solution for forensic real-time detection.In this paper,the recent progress of smartphone-based systems of analytical sensors in forensic real-time detection was reviewed.The analytical principle,the performance of different analytical sensing,and their future perspectives were discussed respectively.

Evaluating the application efficiency of the MHSeqTyper47 kit in kinship identification / 中国法医学杂志

Objective To investigate the application value of the MHSeqTyper47 kit in kinship identification.Methods Multiplexed amplification and library preparation were performed for DNA samples from 113 related individuals by using the MHSeqTyper47 kit.The libraries were sequenced on a MiSeq FGx sequencer,and the data were analyzed using MHTyper for microhaplotype genotyping.The kinship indexes were calculated to evaluate the application efficiency of this kit in kinship identification and compared with those of the GlobalFilerTM kit.Results For the MHSeqTyper47 kit,the CPI values in trio identification were 1.43× 1011～6.15×1018.The CPI values in duo identification were 1.02× 105～1.53× 1013.The CFSI values in full sibling identification were 7.73×101～2.59×1016.Trios,duos and full siblings could be completely distinguished from unrelated pairs.The combined efficiency of these two kits in 2nd-degree kinship identification was 0.466 2.Conclusion The application value of MHSeqTyper47 kit is relatively higher in the identification of lst-degree kinships.If jointly used with the GlobalFilerrM kit,2nd-degree kinship identification could be achieved in some cases.

A nomogram model for predicting malnutrition after a tracheotomy / 中华物理医学与康复杂志

Objective:To explore the risk factors for malnutrition after a tracheotomy and to construct a predictive model useful for its prevention through early intervention.Methods:Clinical data describing 440 tracheotomy patients were subjected to a retrospective analysis. The variables examined were age, sex, etiology, Glasgow Coma Score (GCS), activities of daily living (ADL) score, age-corrected Charlson comorbidity index (aCCI), food intake, swallowing function, incidence of infections, as well as any history of diabetes mellitus, hypertension, smoking or alcohol consumption. Patients identified as being at risk of malnutrition (NRS-2002≥3) were screened using the Nutritional Risk Screening tool (NRS-2002) and the European Society of Clinical Nutrition and Metabolism′s ESPEN2015 criteria. The subjects were thus categorized into a malnutrition group of 343 and a control group of 97. Unifactorial and multifactorial logistic regression analyses were performed, and stepwise regression was applied to include the factors found significant in the unifactorial analysis into the multifactorial logistic regression analysis, and to construct a column-line graph prediction model. The clinical utility of the model was assessed by applying the receiver operator characteristics (ROC) curves, calibration plots and decision curve analysis (DCA).Results:Of the 440 persons studied, 343 (78%) were malnourished. The multivariate logistic regression analysis showed that pulmonary infection, dysphagia, low GCS score and high aCCI score were significant risk factors for malnutrition after a tracheotomy. A prediction nomograph was constructed. After fitting and correcting, the area under the curve (AUC) of the prediction model′s ROC curve was 0.911, the specificity was 80.4%, and the sensitivity was 91.3%. That was significantly higher than the AUCs for pulmonary infection (0.809), dysphagia (0.697), aCCI (0.721) and GCS (0.802). Bootstrap self-sampling was used to verify the model internally. After 1000 samples the average absolute error between the predicted risk and the actual risk was 0.013, indicating good prediction ability. The DCA results demonstrated that the model has substantial clinical applicability across a range of nutritional interventions, particularly for threshold probability values ranging from 0 to 0.96.Conclusion:Pulmonary infection, dysphagia, low GCS score, and high aCCI score are risk factors for malnutrition among tracheotomy patients. The nomogram model constructed in this study has good predictive value for the occurrence of malnutrition among such patients.

Education Concept of Four Famous Traditional Chinese Medicine Doctors in Beijing During Republic of China / 中国实验方剂学杂志

The education concepts of four famous traditional Chinese medicine（TCM） doctors（XIAO Longyou， SHI Jinmo， KONG Bohua and WANG Fengchun） in Beijing during the Republic of China were compared， the commonalities in their education concepts of TCM were sorted out， and the root system of the cultivation and growth of talents in TCM， as well as the direction and way of further development were searched， so as to improve the quality of the inheritance and development of TCM. Based on the systematic review of text and opinion method（SrTO） developed by the centre for evidence-based health care at the Joanna Briggs Institute（JBI） in Australia， this study was conducted to collate and analyze the relevant information， including 14 books， 115 journal papers and 7 documents. Related theory construction and practice of early tutor and academic education have been summarized from college， continuing and tutor education， academic research， examination， and so on. And then the connections and commonalities between the different forms of education in the period were summarized to form a SrTO-based narrative， opinion， text assessment and review instrument（NOTARI） summary table. The findings revealed that these four esteemed TCM doctors and educators， through their substantial influence on TCM education in Beijing， emphasized the importance of classics in teaching and clinical practice， underscored the cultivation of virtue， preserved the traditional teaching model， and championed the establishment of TCM schools. They also put forward novel requisites for the compilation of curricula， teaching materials， and books. Moreover， they advocated for a unified perspective on TCM and western medicine， fostering talent capable of bridging the gap between the two. They encouraged the standardization of TCM teaching examination system， and actively participated in scientific research and book writing. The four TCM doctors transcended the traditional boundaries of TCM practice， fostering a new TCM model of education-clinical-research， and profoundly influencing the contemporary TCM colleges and teacher education.

Analysis of one familial hypokalemic periodic paralysis family with R669H variant of SCN4A gene / 临床神经病学杂志

Objective To investigate the clinical and genetic characteristics of a family with hypokalemic periodic paralysis(HOKPP).Methods The clinical data of one HOKPP family were retrospectively analyzed.Results The proband presented with periodic paralysis,limb weakness and decreased serum potassium(1-2 mmol/L).The proband's father and cousin had similar symptoms.A heterozygous missense variant c.2006G＞A(p.R669H)in SCN4A gene was identified in the proband,his father,younger aunt and cousin using gene detection.However,the variant was absent in his elder aunt and younger uncle.Conclusions The family shows irregular dominant inheritance.The severity,frequency and age of onset of male heterozygotes were different,while female heterozygotes had no clinical phenotype.The study first confirms that the R669H variant in SCN4A gene causes complete penetrance in males and carriers in females in Asian populations.

The influence of demographic and lifestyle factors on blood donation delay among student population: a retrospective study.

Objective: This study analysed blood donation deferral trends, reasons and demographic/lifestyle characteristics among students in Huzhou City. The aim was to understand the health status of students and reduce the deferral rate. Methods: Data on blood donation deferral among students in Huzhou City from 2018 to 2022 were collected and analysed. Deferral trends and main reasons were investigated. Using demographic and lifestyle data from 2,619 cases in 2022, a risk prediction model for deferral was constructed. Results: The deferral rate among students in Huzhou City from 2018 to 2022 was 12.60% (p = 0.000, 95%CI: 12.14-13.06%), showing a significant increasing trend. Temporary deferral was the main reason, with alanine aminotransferase (ALT), blood pressure (BP) and haemoglobin (Hb) as the main deferral factors. ALT had a deferral rate of 5.23% (4.92-5.53%), BP 3.30% (3.06-3.55%), and Hb 2.92% (2.68-3.15%). Demographic and lifestyle characteristics in 2022 showed no significant differences between education level, household registration and deferral rate (p > 0.05). However, age, sex, blood donation history, sleep quality, diet and mental state had variable effects on ALT, BP, and Hb deferrals (p < 0.05). Logistic regression showed that sex, blood donation history, sleep quality, diet and mental status were independent risk factors for ALT deferral (p < 0.05), with odds ratios (ORs) of 5.057, 2.735, 1.594, 3.679, and 1.957, respectively. Age, blood donation history, sleep quality and mental state were independent risk factors for BP deferral (p < 0.05), with ORs of 0.256, 3.658, 6.042, and 1.812, respectively. Gender, blood donation history and diet were independent risk factors for Hb deferral (p < 0.05), with ORs of 0.244, 0.542, and 3.103, respectively. Conclusion: Students' health problems require attention. Effective health education should improve self-health management and pre-donation health behaviour to encourage regular blood donation.

Epidemiological characteristics and risk factors of syphilis among blood donors in Huzhou.

OBJECTIVE: To investigate the epidemiological characteristics and risk factors for syphilis in Huzhou City, and to provide data to support the design of more effective health counselling and screening measures for blood donors. METHODS: A retrospective study was conducted to analyse the demographic characteristics and seropositivity of syphilis among blood donors from 2019 to 2021. The differences in the serological status of syphilis among different populations under different demographic factors were compared, and conditional logistic regression analysis was used to identify the risk factors for syphilis. RESULTS: The seropositivity rate of syphilis among blood donors in Huzhou City was 133/100,000, which decreased year by year. There were significant differences in the syphilis seropositivity rate among different groups in terms of age, education level, occupation, household registration, marital status and blood donation history (P < 0.05). The multivariate logistic regression model showed that all six factors, including age, education level, occupation, household registration, marital status and blood donation history, had significant effects on syphilis infection (P < 0.01), with OR values and 95% CIs of 2. 387 (1.381-4.127), 3.607 (1.609-8.086), 2.784 (1.657-4.679), 5.074 (1.865-13.804), 11.177 (3.481-35.888), and 11.244 (3.940-32.091), respectively. CONCLUSION: There is room for improvement in pre-donation health counselling and screening of high-risk populations. Timely monitoring and updating of demographic data for specific high-risk populations is essential.

The use of human-derived feeder layers for the cultivation of transplantable human epidermal cell sheet to repair second degree burn wounds.

BACKGROUND AND OBJECTIVES: Human epidermal cell sheet (human-ECS) is a feasible treatment option for wound injury. Traditionally, researchers often use murine 3T3 fibroblast cells as feeder layer to support human epidermal cell sheet grafts, thus increase risk to deliver animal-borne infection. To overcome the potential risks involved with xenotransplantation, we develop human foreskin fibroblast cell as feeder layer culture system and investigate the effects of human-ECS on second-degree burn wound healing in mini-pig in order to develop more effective and safer therapies to enhance wound healing in human. MATERIALS AND METHODS: Human epidermal keratinocytes and fibroblasts were isolated from foreskin tissue and were co-cultured to manufacture human-ECS. The cell morphology was monitored with phase-contrast microscopy, the stem cell markers were assessed by flow cytometry, and by colony-forming efficiency (CFE) assay. The structure of human-ECS was observed by hematoxylin and eosin staining. Expression of cytokines in human-ECS was confirmed by enzyme-linked immunosorbent assay. Second-degree burn wounds were created on the dorsal of miniature pig to evaluate the effect of oil gauze, oil gauze combined with commercial epidermal growth factor (EGF) cream, and oil gauze combined with human-ECS. Wound healing rate, histological examination, and Masson staining were measured to observe the wound repair efficacy. Real-time PCR and Western blot were utilized to detect the expression level of EGF and interleukin 6 (IL-6). RESULTS: Stratified human-ECS with 6-7 layers of epidermal cells was successfully cultivated with human-derived feeder cells, in which epidermal cell highly expressed CD49f and CFE was 3% ± 0.45%. Application of human-ECS induced a higher wound healing rate than commerical EGF cream and oil gauze control. The expression of EGF in human-ECS group was higher than those in the other groups; however, the expression of IL-6 was significantly decreased at day 14 by human-ECS treatment group. CONCLUSIONS: Human-derived feeder cells are suitable for cultivation of human-ECS, avoiding pathogen transmission. Human-ECS could enhance second-degree burn wound healing, and its promoting effect involved secreting a variety of cytokines to regulate tissue reparative process.

Genetic variation analysis of Human Papillomavirus 16 E4 and L2 in women with cervical infection in Xinjiang Uygur Autonomous Region / 安徽医科大学学报

Objective @#To explore the nucleotide variation and protein amino acid changes of E4 and L2 genes of Human Papillomavirus 16 (HPV16) , and to analyze the evolutionary characteristics of HPV16 virus.@*Methods @# 40 HPV16 infection⁃positive cervical exfoliated cells samples and tissue cell samples were collected from hospital , viral DNA was extracted , Sanger sequencing perform in cervical exfoliated cells DNA and high⁃throughput sequencing technology sequenced in cervical tissues DNA for E4 and L2 genes of HPV16 , HPV16 E4 and L2 gene phylogenetic evolution trees were constructed , and variation of HPV16 E4 and L2 genes were analyzed. @*Results @#There were 72 HPV16 E4 variant samples with nucleotide variants (4 missense mutations and 7 synonymous mutations) at 10 sites , HPV16 L2 gene variants in 74 samples , and nucleotide variants (23 missense mutations and 18 synonymous mutations) at 40 sites. The variation frequency of T4177C , A4288C and A4654C in cervical cancer was significantly higher than that in non⁃cervical cancer, and the difference was statistically significant (P < 0. 05) . @*Conclusion@#① The main HPV16 virus strains in Xinjiang are European strains , and a few are Asian strains. ② The mutation frequency of T4177C , A4288C and A4654C in HPV16 L2 gene is higher than that in non⁃cervical cancer, and G4181A is related to the Asian strain.

A research on epilepsy source localization from scalp electroencephalograph based on patient-specific head model and multi-dipole model / 生物医学工程学杂志

Accurate source localization of the epileptogenic zone (EZ) is the primary condition of surgical removal of EZ. The traditional localization results based on three-dimensional ball model or standard head model may cause errors. This study intended to localize the EZ by using the patient-specific head model and multi-dipole algorithms using spikes during sleep. Then the current density distribution on the cortex was computed and used to construct the phase transfer entropy functional connectivity network between different brain areas to obtain the localization of EZ. The experiment result showed that our improved methods could reach the accuracy of 89.27% and the number of implanted electrodes could be reduced by (19.34 ± 7.15)%. This work can not only improve the accuracy of EZ localization, but also reduce the additional injury and potential risk caused by preoperative examination and surgical operation, and provide a more intuitive and effective reference for neurosurgeons to make surgical plans.

Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).@*METHODS@#A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.@*RESULTS@#The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).@*CONCLUSIONS@#Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.

Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations.@*METHODS@#A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University.@*RESULTS@#The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy.@*CONCLUSIONS@#Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.

Herbal Textual Research on Piperis Kadsurae Caulis in Famous Classical Formulas / 中国实验方剂学杂志

Through consulting the ancient materia medica and medical books， combined with modern literature， this paper made a textual research on the name， origin， producing area， harvesting time and processing method of Piperis Kadsurae Caulis， in order to provide basis for the development of the famous classical formulas containing this herb. According to textual research， it is shown that the earliest name for Piperis Kadsurae Caulis as medicine was Nanteng in Bencao Shiyi， and there were other names such as Dinggongteng and Shinanteng in the ancient materia medica. The name of Haifengteng should appear in the Ming dynasty. Before the Song dynasty， the origin of Piperis Kadsurae Caulis was probably derived from caulis of Piper wallichii. After the Song dynasty， the main origins should be some species in Piper， such as P. kadsura and P. hancei， and its origin in the successive editions of Chinese Pharmacopoeia was only P. kadsura. Combining the original plant research， market survey and distribution of wild resources， it is suggested that the Haifengteng used in the famous classical formulas apart form the P. kadsura， the P. hancei should be add as original plant. Due to climate change and the heat-loving habit of Piper， the producing area of Haifengteng gradually moved from the Qinling Mountains to the southern areas rich in Piper， and Quanzhou area of Fujian province has been recommended since the Ming dynasty. The harvesting period of Piperis Kadsurae Caulis is from July to August in the lunar calendar， the above-ground parts are dried by removing fibrous roots， thin stems and leaves. In the past dynasties， there are few records on the processing of this herb， so it is suggested that Piperis Kadsurae Caulis in famous classical formulas without special processing requirements should be used as raw products.