Zoledronic acid epigenetically alleviates high-glucose-suppressed osteogenic differentiation of MC3T3-E1 cells.

OBJECTIVE: Due to the impact of excessive glucose on osteogenic differentiation, diabetic osteopathy frequently results in skeletal fragility, osteoporosis, and bone pain. Zoledronic acid, a bisphosphonate (BP) that effectively inhibits osteoclastic bone resorption is given yearly to improve bone mineral density (BMD) in patients with osteoporosis. However, the detailed molecular mechanisms remained unclear. This study investigates the possible pathways by which zoledronic acid regulates osteogenesis when blood glucose levels are high. MATERIALS AND METHODS: MC3T3-E1 cells were treated with one mM zoledronic acid or not in a standard or high glucose culture medium. A quantitative polymerase chain reaction (qPCR) assay was utilized to assess the expression of the target candidate genes, including RUNX2, MALAT1, miR-133, miR-20a, and miR-204. RESULTS: In a high-glucose condition, zoledronic acid treatment significantly lowered MALAT1 (p < 0.0001) and miR-20a (p < 0.0001) expression. Conversely, in a high-glucose condition, RUNX2, miR-133, and miR-204 expressions were found to be significantly increased in the zoledronic acid treatment group as compared to no treatment (all p < 0.0001). CONCLUSIONS: In conclusion, under a high-glucose environment, zoledronic acid can modulate the expression of the RUNX2 transcription factor through epigenetic regulation.

[Mechanism of intestinal injury induced by WNT2B high-expressed fibroblasts in Crohn's disease].

Objective: To explore the mechanism of intestinal tissue damage induced by macrophages activated by WNT2B high-expressed fibroblasts. Methods: This study involved biological information analysis, pathological tissue research and cell experimental research. The biological information of the colon tissue from the children with inflammatory bowel disease in previous study was analyzed again with single-cell sequencing. The pathological tissues were collected by colonoscopy from 10 children with Crohn's disease treated in the Department of Gastroenterology of Guangzhou Women and Children's Medical Center from July 2022 to September 2022. According to the findings of colonoscopy, tissues with obvious inflammation or ulceration were classified as the inflammatory group, while tissues with slight inflammation and no ulceration were classified as the non-inflammatory group. HE staining was performed to observe the pathological changes of the colon tissues. Macrophage infiltration and CXCL12 expression were detected by immunofluorescence. In terms of cell experiments, fibroblasts transfected with WNT2B plasmid or empty plasmid were co-cultured with salinomycin treated or non-treated macrophages, respectively; the expression of proteins through Wnt classical pathway were detected by western blotting. Macrophages treated with SKL2001 were used as the experimental group, and those with phosphate buffer as the control group. The expression and secretion of CXCL12 in macrophages were detected by quantitative Real-time PCR and enzyme-linked immunosorbent assay (ELISA). T-test or rank sum test were used for the comparison between groups. Results: Single-cell sequencing analysis suggested that macrophages were the main cells in inflammatory bowel disease colon tissue, and there was interaction between WNT2B high-expressed fibroblasts and macrophages. HE staining of the 10 patients ((9.3±3.8) years old, 7 males and 3 females) showed that the pathological score of colon tissue in the inflammatory group was higher than that in the non-inflammatory group (4 (3, 4) vs. 2 (1, 2) points, Z=3.05, P=0.002). Tissue immunofluorescence indicated that the number of infiltrating macrophages in the inflammatory group was significantly higher than that in the non-inflammatory group under high power field of view (72.8±10.4 vs.8.4±3.5, t=25.10, P<0.001), as well as the number of cells expressing CXCL12 (14.0±3.5 vs. 4.7±1.9, t=14.68, P<0.001). In cell experiments, western blotting suggested an elevated level of glycogen synthase kinase-3ß phosphorylation in macrophages co-cultured with fibroblast transfected with WNT2B plasmid, and salinmycin could reverse this change. Real-time PCR suggested that the transcription level of CXCL12 in the experimental group was higher than that in the control group (6.42±0.04 vs. 1.00±0.03, t=183.00, P<0.001), as well as the expression and secretion of CXCL12 by ELISA ((465±34) vs. (77±9) ng/L, t=13.21, P=0.006). Conclusion: WNT2B high-expressed fibroblasts can secrete WNT2B protein and activate the Wnt classical signaling pathway thus enhancing the expression and secretion of CXCL12 in macrophages, inducing the development of intestinal inflammation of Crohn's disease.

Issue 2 - "Update on adverse respiratory effects of indoor air pollution". Part 2): Indoor air pollution and respiratory diseases: Perspectives from Italy and some other GARD countries.

OBJECTIVE: to synthesize the Italian epidemiological contribution to knowledge on indoor pollution respiratory impact, and to analyze the perspective of some GARD countries on the health effects of indoor air pollution. RESULTS: Italian epidemiological analytical studies confirmed a strong relationship between indoor air pollution and health in general population. Environmental tobacco smoke, biomass (wood/coal) fuel for cooking/heating and indoor allergens (house dust mites, cat and dog dander, mold/damp) are the most relevant indoor pollution sources and are related to respiratory and allergic symptoms/diseases in Italy and in other GARD countries such as Mexico, Brazil, Vietnam, India, Nepal and Kyrgyzstan. Community-based global health collaborations are working to improve prevention, diagnosis and care of respiratory diseases around the world, specially in low- and middle-income countries, through research and education. CONCLUSIONS: in the last thirty years, the scientific evidence produced on respiratory health effects of indoor air pollution has been extensive, but the necessity to empower the synergies between scientific community and local administrations remains a challenge to address in order to implement effective interventions. Based on abundant evidence of indoor pollution health effect, WHO, scientific societies, patient organizations and other members of the health community should work together to pursue the GARD vision of "a world where all people breathe freely" and encourage policy makers to increase their engagement in advocacy for clean air.

[Fibroblasts overpressing WNT2b cause impairment of intestinal mucosal barrier].

OBJECTIVE: To investigate the mechanism by which fibroblasts with high WNT2b expression causes intestinal mucosa barrier disruption and promote the progression of inflammatory bowel disease (IBD). METHODS: Caco-2 cells were treated with 20% fibroblast conditioned medium or co-cultured with fibroblasts highly expressing WNT2b, with the cells without treatment with the conditioned medium and cells co-cultured with wild-type fibroblasts as the control groups. The changes in barrier permeability of Caco-2 cells were assessed by measuring transmembrane resistance and Lucifer Yellow permeability. In Caco-2 cells co-cultured with WNT2b-overexpressing or control intestinal fibroblasts, nuclear entry of ß-catenin was detected with immunofluorescence assay, and the expressions of tight junction proteins ZO-1 and E-cadherin were detected with Western blotting. In a C57 mouse model of dextran sulfate sodium (DSS)-induced IBD-like enteritis, the therapeutic effect of intraperitoneal injection of salinomycin (5 mg/kg, an inhibitor of WNT/ß-catenin signaling pathway) was evaluated by observing the changes in intestinal inflammation and detecting the expressions of tight junction proteins. RESULTS: In the coculture system, WNT2b overexpression in the fibroblasts significantly promoted nuclear entry of ß-catenin (P < 0.01) and decreased the expressions of tight junction proteins in Caco-2 cells; knockdown of FZD4 expression in Caco-2 cells obviously reversed this effect. In DSS-treated mice, salinomycin treatment significantly reduced intestinal inflammation and increased the expressions of tight junction proteins in the intestinal mucosa. CONCLUSION: Intestinal fibroblasts overexpressing WNT2b causes impairment of intestinal mucosal barrier function and can be a potential target for treatment of IBD.

[Research progress on moderate and deep sedation during wound dressing change in pediatric burn patients].

Moderate and deep sedation can effectively relieve or eliminate the pain and body discomfort during wound dressing change in pediatric burn patients, relieve anxiety, agitation, and even delirium of the children, reduce the metabolic rate of the children, make them in a quiet, comfortable, and cooperative state, which is conducive to the smooth completion of dressing change. This paper summarized the three aspects of moderate and deep sedation in pediatric burn patients, including the overview, main points of implementation, and effects, and further introduced the moderate and deep sedation medication regimens for different routes of administration, as well as the content of evaluation and monitoring. Suggestions on the prevention and management of related complications and the management of moderate and deep sedation implementation procedures were put forward, in order to provide references for the development of moderate and deep sedation for wound dressing change in pediatric burn patients in China.

FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation.

Cancers arising from the bladder urothelium often exhibit lineage plasticity with regions of urothelial carcinoma adjacent to or admixed with regions of divergent histomorphology, most commonly squamous differentiation. To define the biologic basis for and clinical significance of this morphologic heterogeneity, here we perform integrated genomic analyses of mixed histology bladder cancers with separable regions of urothelial and squamous differentiation. We find that squamous differentiation is a marker of intratumoral genomic and immunologic heterogeneity in patients with bladder cancer and a biomarker of intrinsic immunotherapy resistance. Phylogenetic analysis confirms that in all cases the urothelial and squamous regions are derived from a common shared precursor. Despite the presence of marked genomic heterogeneity between co-existent urothelial and squamous differentiated regions, no recurrent genomic alteration exclusive to the urothelial or squamous morphologies is identified. Rather, lineage plasticity in bladder cancers with squamous differentiation is associated with loss of expression of FOXA1, GATA3, and PPARG, transcription factors critical for maintenance of urothelial cell identity. Of clinical significance, lineage plasticity and PD-L1 expression is coordinately dysregulated via FOXA1, with patients exhibiting morphologic heterogeneity pre-treatment significantly less likely to respond to immune checkpoint inhibitors.

[A multicenter epidemiological study of acute bacterial meningitis in children].

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum ß-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.

[Combined resection of thoracic and abdominal organ clusters: a series of 50 cases].

Objective: To examine the technique and effect of combined thoracic and abdominal organ clusters resection. Methods: From February 2019 to August 2021, totally 50 cases of combined thoracoabdominal organ cluster resection were completed at Transplant Medical Center, the Second Affiliated Hospital of Guangxi Medical University from donation after brain death donors. There were 47 males and 3 females, aging (34.8±12.3) years (range: 5 to 55 years). The length of hospital stay(M(IQR)) was 4(4) days (range: 2 to 43 days), the length of tube time was 4(2) days (range: 1 to 43 days). Through the midsternal incision and the abdominal grand cross incision, the cold perfusion was performing simultaneously when the perfusion lines of each target organ was established respectively. The combined resection was performed with the diaphragm as the boundary and the organ cluster as the unit. The heart and lung were separated on site and sent to the transplant hospital, and the abdominal organ cluster was directly preserved and returned to our hospital for further separation and repair. Results: Totaly 21 hearts, 47 pairs of lungs, 49 livers, 47 pairs of kidneys and 11 pancreas were harvested by this surgical treatment. The resection time was (32.6±6.5) minutes (range: 19 to 50 minutes), with no hot ischemia time. There was no accidental injury that affected organ quality and function. Heart transplantation was performed in 17 cases, combined heart-kidney transplantation in 2 cases, double lung transplantation in 43 cases, single lung transplantation in 6 cases, liver transplantation in 41 cases, combined liver-pancreas-duodenal cluster transplantation in 1 case, combined liver-kidney transplantation in 3 cases, combined pancreas-kidney transplantation in 9 cases, and kidney transplantation in 74 cases. Conclusion: Simultaneous perfusion and combined resection of thoracic and abdominal organ clusters for donation after brain death donors are feasible and effective.

[Relationship between prognosis and different surgical treatments of zygomatic defects: A retrospective study].

OBJECTIVE: To evaluate the effect and summarize the characteristics of different treatment methods in repairing zygomatic defect. METHODS: A total of 37 patients with zygomatic defect were reviewed in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from August 2012 to August 2019. According to the anatomical scope of defect, the zygomatic defects were divided into four categories: Class 0, the defect did not involve changes in zygomatic structure or continuity, only deficiency in thickness or projection; Class Ⅰ, defect was located in the zygomatic body or involved only one process; Class Ⅱ, a single defect involved two processes; Class Ⅲa, referred to a single defect involving three processes and above; Class Ⅲb, referred to zygomatic defects associated with large maxillary defects. The etiology, defect time, defect size and characteristics of zygomatic defects, the repair and reconstruction methods, and postoperative complications were collected and analyzed. Postoperative computed tomography (CT) data were collected to evaluate the outcome of zygomatic protrusion. Chromatographic analysis was used to assess the postoperative stability. RESULTS: Among the causes of defects, 25 cases (67.57%) were caused by trauma, and 11 cases (29.73%) were of surgical defects following tumor resection. We performed autologous bone grafts in 19 cases, 6 cases underwent vascularized tissue flap, 5 cases underwent external implants alone, and 7 cases underwent vascularized tissue flap combined with external implants. After the recovery of the affected side, the average difference of the zygomatic projection between the navigation group and the non-navigation group was 0.45 mm (0.20-2.50 mm) and 1.60 mm (0.10-2.90 mm), with a significant difference (P=0.045). Two patients repaired with titanium mesh combined with anterolateral thigh flap had obvious deformation or fracture of titanium mesh; 2 patients with customized casting prosthesis had infection after surgery and fetched out the prosthesis finally. CONCLUSION: Autologous free grafts or alloplastic materials may be used in cases without significant structural changes. Pedicle skull flap or vascularized bone tissue flap is recommended for zygomatic bone defects with bone pillar destruction, chronic inflammation, oral and nasal communication or significant soft tissue insufficiency. Titanium mesh can be used to repair a large defect of zygomatic bone, and it is suggested to combine with vascularized bone flap transplantation.

Pathological characterization and clinical outcome of penile intraepithelial neoplasia variants: a North American series.

Penile intraepithelial neoplasia (PeIN) is classified as human papillomavirus (HPV)- and non-HPV-related. This classification is associated with distinct morphologic subtypes. The natural history and prognosis of PeIN subtypes are not well known. This study aims to evaluate clinicopathological features, HPV status, and outcome of PeIN subtypes. Eighty-two lesions from 64 patients with isolated PeIN were retrospectively reviewed. Mean age was 59 years. Lesions were multicentric in 34% of patients and affected glans (33%), shaft (26%), and foreskin (20%). Histologically, 22% of patients had coexisting lesions, classified as hybrid and mixed. HPV-related PeIN (97%) included basaloid (59%), warty (8%), warty-basaloid (8%), hybrid (19%) and mixed (3%) types. P16 and HPV positivity occurred in 99% and 82% of lesions, respectively. HPV 16 was more common in basaloid PeIN. Multiple genotypes were detected in 35%, more commonly in hybrid PeIN (P = 0.051). Positive margins occurred in 63% of excisions. PeIN recurred in 48% of excisions and 30% of overall repeated procedures, and progression to invasive carcinoma occurred in 2%. At follow-up, 86% of patients had no evidence of disease and 12% were alive with disease. Lichen sclerosus occurred in non-HPV and HPV-related PeIN (100% and 47%).In conclusion, HPV-related and, more specifically basaloid PeIN were the predominant types and preferentially associated with HPV 16. While PeIN had a high recurrence rate, there was a slow and infrequent progression to invasive or metastatic carcinoma with multimodal treatments. Additional studies are needed to understand biology and natural history of PeIN.

The value of soluble suppression of tumorigenesis-2 (sST2) in the maintenance of hemodialysis patients with heart failure.

BACKGROUND: Patients with end-stage renal disease are prone to develop heart failure (HF). The N-terminal pro-brain natriuretic peptide (NT-proBNP, BNP) is regarded as the gold standard for diagnosing HF. However, its prognostic sensitivity in patients with end-stage renal disease is sub-optimal. Soluble suppression of tumorigenesis-2 (sST2) has been well studied in HF but rarely in patients with maintenance hemodialysis (MHD). This study aimed to evaluate the value of sST2 in predicting HF in MHD patients. METHODS: Twenty-three patients with New York Heart Association (NYHA) class III-IV were included in the HF group and 88 NYHA class I-II patients in the non-heart failure (NHF) group. sST2 and laboratory indexes were compared between the two groups. RESULTS: The HF group, compared with the NHF group, presented with higher sST2, more advanced age, higher incidence of coronary heart disease (CHD), left ventricle end-diastolic diameter (LVEDD), and pulmonary artery pressure (PAP), and unchanged parathyroid hormone (iPTH). The HF group also had lower ejection fraction (EF), uric acid, inorganic phosphorus, 25-OH VitD3, and serum albumin. Multivariate logistic regression indicated that age, BNP, and sST2 were independent risk factors of HF in MHD patients. Spearman analysis defined that sST2 was positively correlated with PAP (r =0.283, p =0.003) and C-reactive protein (r =0.354, p <0.001); and negatively correlated with sex (r =-0.255, p =0.007), albumin (r =-0.366, p <0.001), uric acid (r =-0.213, p =0.025), 25-OH VitD3 (r =-0.216, p =0.04), calcium (r =-0.219, p =0.021), and inorganic phosphorus (r =-0.256, p =0.007). Receiver operating characteristic curve analysis determined a positive association between BNP and sST2 (r =0.373, p <0.001), with the area under the curve (AUC) of BNP being 0.822 (sensitivity: 0.783, specificity: 0.830) and the AUC of sST2 being 0.841 (sensitivity: 0.913, specificity: 0.761). The AUC of sST2 was 0.841, and the cut-value was 42.840 (sensitivity: 0.913, specificity: 0.761). CONCLUSION: sST2 can predict HF in MHD patients and facilitate early diagnosis and prevention of HF in MHD patients. HIPPOKRATIA 2022, 26 (1):19-24.

[Lesion removal plus whole breast exploration and washing plus micro-plastic procedures in the treatment of granulomatous lobular mastitis: a randomized controlled study].

Objective: To examine the effect of"lesion removal plus whole breast exploration and washing plus micro-plastic surgery"in granulomatous lobular mastitis. Methods: A single-center prospective randomized controlled study method was used to enroll patients diagnosed with granulomatous lobular mastitis for whom surgical procedures were projected from March 2017 to September 2019 at Department of Thyroid and Breast Surgery, Zhongnan Hospital of Wuhan University. The sample size is determined by the superiority test. Based on the literatures and the previous work, the two groups require 97 cases. Fifty-two patients underwent"lesion removal+whole breast exploration and washing plus micro-plastic surgery"(observation group). Forty-five cases underwent"empirical breast lesion resection plus fascia tissue flap plasty plus nipple and areola correction"(control group). The primary study endpoint is the recurrence rate, and the secondary study endpoints include surgical complications, incision healing time, and postoperative patient satisfaction. Independent sample t test, Wilcoxon rank-sum test, χ² test and Fisher exact test were used for comparison between groups. Results: All procedures were completed successful, with no severe complications. All patients were followed up for (15.2±1.9) months (range: 12 to 24 months). There were no significant differences in incidence of postoperative complications (7.7% (4/52) vs. 6.7%(3/45), P=1), drainage time ((8.6±0.6) days vs. (8.4±0.8) days, t=1.921, P=0.053) and hospital stay ((7.7±0.6) days vs. (7.6±0.5) days, t=1.633, P=0.102) between the two groups. The recurrence rate of the observation group was lower significantly than that of the control group (3.8% (2/52) vs. 24.4%(11/45), χ²=8.819, P=0.003). The observation group had better cosmetic effects (Z=-2.657, P=0.008) and patient satisfaction than control group (Z=-5.730, P=0.000). Conclusion: The "lesion removal plus whole breast exploration and flushing plus micro-plastic surgery" has a good therapeutic effect and cosmetic value for patients with refractory granulomatous lobular mastitis.

Taurine Reduces Liver Damage in Non-Alcoholic Fatty Liver Disease Model in Rats by Down-Regulating IL-9 and Tumor Growth Factor TGF-ß.

The study employed a rat model to examine the effects of taurine (Tau) on prevention and therapy of non-alcoholic fatty liver disease (NAFLD). In model rats maintained on a high-fat diet (HFD), the serum levels of ALT, AST, triglycerides, cholesterol, and LDL were higher than the corresponding levels in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, the serum levels of AST and triglycerides were lower than in HFD rats (p<0.05). In HFD rats, diffuse fatty degeneration and infiltration with inflammatory cells was observed in the liver; in the ileal mucosa, the villi were fractured or absent, the epithelium was exfoliated and infiltrated with inflammatory cells. The levels of TGF-ß, IL-9, and their mRNA in the liver and ileal mucosa of HFD rats were significantly higher than in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, these levels were significantly lower than in HFD rats (p<0.05). Thus, TGF-ß and IL-9 can be implicated in NAFLD genesis, while Tau can preventively or therapeutically diminish the damage to the liver and ileal mucosa in rats with this disease by down-regulating the expression of TGF-ß and IL-9.

[Cognitive and gait dysfunction in the elderly caused by age-related cerebral small vessel disease and idiopathic normal pressure hydrocephalus: a case series of three patients].

Three cases with age-related cerebral small vessel disease and normal pressure hydrocephalus in the Department of Neurology of Sun Yat-sen University were retrospectively reviewed. All the patients exhibited gait disturbance, cognitive impairment and urinary incontinence. Meanwhile, the Craniocerebral imaging demonstrated cerebral small vessel disease and communicating hydrocephalus. The cerebralspinal fluid (CSF) Aß42 levels decreased, and apolipoprotein E (APOE) genotypes were ε3/ε4,ε3/ε3,ε2/ε3, respectively. After treatment in an all-cause individualized manner, the symptoms of 3 patients were stable or improved.

[Identification of a novel mutation of SOX10 gene and analysis of the phenotype].

Objective: To explore the clinical features and pathogenic mechanisms of a special syndrome with congenital sensorineural hearing loss, albinism, heterochromia iridis, nystagmus and myelin dysplasia. Methods: Detailed medical history, systematic audiology tests, ophthalmic and neurological examinations were carried out to analyze the clinical features of the child, and further molecular genetic tests including chromosome karyotype analysis, and deafness gene screening were conducted. Results: A new de novo heterozygous mutation (c.336G>T/p.Met112Ile) was detected in the child, while both his parents were demonstrated to be wild-type and symptom free. The analysis of clinical features indicated the diagnosis of PCW syndrome. Conclusion: This study identified a new mutation of SOX10 gene, which enriched the mutation spectrum of this gene. And the analysis of clinical characteristics of this patient also expanded the phenotype of this gene. This study provided a reference for clinical diagnosis and genetic diagnosis of PCW syndrome.

[Study on molecular of anti-tumor mechanism of Forsythia suspensa based on molecular docking and network pharmacology].

In this paper, the possible molecular mechanism of Forsythia suspensa for the anti-tumor effect was investigated through the network pharmacology and molecular docking. The main components of F. suspensa were obtained by literature mining and TCMSP database. Cancer-related genes were collected with use of GAD and OMIM databases. The interaction network of Compounds-Targets-Pathways was constructed through Cytoscpe software. The targets were analyzed by GO and KEGG means in DAVID database, and the KEGG signal pathways were visualized. Component-Target network analysis results were verified by PyRx molecular docking. The results showed that a total of 26 main components of F. suspensa may act on key targets such as AKT1, IL6, ESR1, EGFR, EGF and CCND1, and were involved in 20 signal pathways. Molecular docking analysis showed that hydrogen bonding, hydrophobic action and Pi-cation bonding maybe the main forms of interaction. In this study, we revealed the anti-tumor effect of F. suspensa through the network of Compounds-Targets-Pathways and molecular docking verification, providing reference and guidance for systematically elucidating the anti-tumor molecular mechanism of the main components of F. suspensa.

[Effect of bone marrow mesenchymal stem cells on paraquat-induced pulmonary fibrosis in rats].

Objective: To study the effect of the injected bone marrow mesenchymal stem cells (BMSC) on rats with pulmonary fibrosis induced by paraquat (PQ) during different poisoning periods and explore the potential mechanism. Methods: From October to December 2018, BMSCs of SPF SD rats were isolated and purified by whole-bone marrow adherent culture method and cultured to the Third Generation (P3) . The surface antigens CD29, CD90, CD45 and CD34 of P3 BMSC were detected by Flow cytometry, the formation of alkaline phosphatase (ALP) , calcium nodules and fat droplets were observed by ALP, Alizarin Red staining and oil red O staining. At the same time, 36 SPF male rats were randomly divided into 6 groups: NC Group (Blank Control Group, injected with the same amount of saline) and PQ group (PQ model group, injected with 20% PQ solution 18 mg/kg intraperitoneally) , bMSC-A group, BMSC-B group, BMSC-C group and BMSC-D group were injected with BMSC suspension 1×10(6) cells/mice at 3 h、3 d、7 d and 14 d after PQ poisoning. After 28 days, the rats were killed, the lung organ coefficients were calculated, the hydroxyproline (HYP) content in lung tissue was calculated by alkaline hydrolysis, and the lung injury and fibrosis were observed by HE and Masson staining, serum TGF-1、TNF-α、MMP-9 and TIMP-1 were detected by Elisa. Results: High Purity BMSCs were successfully isolated and obtained. The P3 BMSC generation was positive expression of CD29、CD90、and negative expression of CD34、CD45, and had the potential of osteogenic and adipogenic differentiation. The results of HE staining and Masson staining showed that the alveolar structure in NC group was intact and homogeneous, in PQ group, the alveolar structure was severely damaged and a lot of collagen fibers and fibroblasts were deposited, and the degrees of lung injury in each BMSC intervention group were obviously less than in PQ group, in BMSC-A group and BMSC-B group, the degrees of reduction were obvious. Compared with NC group, the Lung organ coefficient, HYP content in lung tissue and TGF-ß1, TIMP-1 levels in serum were significantly higher in PQ group (P<0.05) , while TNF-α and MMP-9 had no significant difference (P>0.05) . Compared with PQ group, the lung organ Coefficients, HYP, TGF-1 and TIMP-ß1 in BMSC-A and BMSC-B groups were lower than those in PQ group (P<0.05) . The Lung organ coefficients, TGF-ß1 and TIMP-1 in BMSC-C and BMSC-D groups were lower than those in PQ group, there was no significant difference (P>0.05) . Conclusion: Early BMSC injecting can alleviate pulmonary fibrosis induced by PQ. The mechanism may be that BMSC can reduce pulmonary fibrosis through reducing the level of TGF-ß1 and regulating the balance of TIMP-1/MMP-9, threrby reducing inflammatory damage and increasing the degradation of extracellular matrix (ECM) .