[Research progress on virulence factors of hypervirulent Klebsiella pneumoniae].

Hypervirulent Klebsiella pneumoniae, short for hvKP, is a hypervirulent variant of classical Klebsiella pneumoniae, which accounts for serious infection in healthy people, exhibits strong pathogenicity, high mortality and poor prognosis. At present, hvkp is of high prevalence all over the world, and the infection rate shows a continuous upward trend, which brings great challenges to public health security and clinical treatment. This paper summarized the research progress on virulence factors of hvkp, such as capsular polysaccharides, siderophore, lipopolysaccharide, adhesins and recently discovered Type Ⅵ secreting system, and aimed to deepen the understanding and recognition of hvKP.

[Evaluation of classification of petroclival meningiomas and proposed selection of microsurgical approach: a single center experience of 179 cases].

Objective: To evaluate the classification of petroclival meningiomas(PCM), proposed selection of microsurgical approach and therapeutic outcomes. Methods: Retrospectively analyzed clinical data of 179 cases of PCM from Department of Neurosurgery, Xiangya Hospital, Central South University between January 2011 and November 2020. There were 28 males and 151 females with an age of(49.9±10.2) years(range: 22 to 75 years) and the tumor size of(44.8±10.3)mm(range: 15 to 80 mm). The mean duration of symptom(M(QR)) was 18.0(40.6)months(range:1 week to 320 months) and the mean preoperative Karnofsky performance scale(KPS) was 78.6±13.3(range: 40 to 100). The PCM were classified into 5 types according to the difference in the origin of dural attachment, involvement of adjacent structures and growth patterns through preoperative MRI. The surgical approaches were selected based on the proposed classification, and the clinical characteristics, surgical record, and follow-up data of each type were reviewed. Results: The PCM were divided into clivus type(CV, 4 cases), petroclival type(PC, 60 cases), petroclivosphenoidal type(PC-S, 62 cases), sphenopetroclival type with 2 subtypes(S-PC, 50 cases) and central skull base type(CSB, 3 cases). All of 176 cases were obtained microsurgical treatment except CSB type. The gross total resection reached in 124 cases(70.5%) with 112 cases of retrosigmoid approach(RSA), 27 cases of subtemporal transtentorial transpetrosal approach, 13 cases of pretemporal trancavernous anterior transpetrosal approach(PTCA), 12 cases of extended pterional transtentorial approach(EPTA) and presigmoid combined supra-infratentorial approach, respectively. The RSA could be adopted in both of CV type and PC type and most of PC-S type(71.0%). S-PC subtype Ⅰ and subtype Ⅱ were mainly underwent EPTA(40.8%) and PTCA(52.2%), respectively. Seventy-two cases(40.9%) gained new neurological dysfunctions mainly with the cranial nerve paralysis. The postoperative morbidity and complications were recovered or improved with conservative and positive symptomatic and supportive treatment. There was no intraoperative and postoperative death case. One hundred and sixty four cases(93.2%) of operative patients were followed with the duration of 24(48)months(range:3 to 108 months). Tumor recurrence and progress were identified in 14 cases(10.4%) and 14 cases(28.6%), respectively. Compared with postoperative neurological status, 89 patients(54.3%) had improved and 38 patients(23.2%) were still suffering various degrees of neurological dysfunctions during the follow-up. The recent KPS was 84.2±11.4(range: 50 to 100) without statistical difference from preoperative KPS(t=-1.356,P=0.125). As for each type, there were statistically significant differences in brain stem edema(χ2=3.482,P=0.038), gross total resection(χ2=9.127,P=0.001), surgical duration(F=8.954, P=0.013), postoperative length of stay(F=3.652, P=0.025), postoperative complications(χ2=1.550,P=0.024), postoperative KPS(F=2.856, P=0.042) and tumor recurrence/progress(χ2=4.824,P=0.013). Conclusion: The precise and comprehensive classification of PCM and specific individual treatment strategy are benefit to evaluate the diverse clinical prognosis, choose optimal surgical approaches, elevate gross total resection, diminish neurological dysfunctions and restraint tumor recurrence, so as to improve the quality of life for patients.

[Research progress on the regulation mechanism of Pseudomonas aeruginosa biofilm].

Pseudomonas aeruginosa is one of the common multidrug-resistant bacteria in the clinic. Because it can produce a "protective" biofilm, it can affect the penetration and killing efficacy of antibacterial drugs, leading to the formation of a persistent and persistent chronic infection in the host. Biofilms make Pseudomonas aeruginosa resistant to antibacterials and evasive to the host's immune system. Therefore, traditional conventional antibacterials are difficult to achieve effective bactericidal treatment. Understanding the process of P. aeruginosa biofilm formation and the regulatory mechanisms that affect biofilms can provide ideas and methods for our future research on new antibacterial drugs.

Effects of exercise on sex hormones and expression of relevant genes in the hypothalamus in obese mice.

This study aimed to investigate the effect of different exercise loads on sex hormones and expressions of relevant genes in hypothalamus in obese mice. Sixty weaning male C57BL/6 mice were used as subjects. Among them, 15 mice were randomly classified into the normal diet group (CON group), and the remaining 45 mice into high-fat diet group (MOB group). The obesity was successfully achieved by high-fat diet 10 weeks later. Then the rats were randomly divided into three groups based on weight, namely, obesity control group (OBC group), obesity with moderate-intensity exercise group (MOBC group), and obesity with high-intensity exercise group (HOBC group), with 15 mice in each group. Mice in the MOBC group and HOBC group were offered 8 weeks of swimming training, and the exercise time increased incrementally until 2 h and 4 h per day. After the training was over, ELISA method was used to determine the serum levels of Adiponectin (Adipo), luteotropic hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T). Real-time PCR was implemented to detect the transcriptional levels of genes of Adipo and other relevant proteins in the hypothalamus. The result showed that compared with the CON group, there was a significant reduction in the serum levels of Adipo, LH, FSH and T in the OBC group (P<0.05). As compared with the OBC group, the serum levels of Adipo, LH, FSH and T increased significantly in the OBC group (P<0.05). There was a significant increase in the transcriptional levels of Adipo, Adipo receptor 1 (Adipo R1), and AMP-activated protein kinase (AMPK) in the OBC group (P<0.05) compared to in the CON group; meanwhile, the transcriptional levels of kisspeptin (Kiss) and gonadotropin-releasing hormone (GnRH) decreased significantly (P<0.05). In conclusion, long-term moderate-intensity exercise could improve the negative effect of obesity on sex development. Long-term high-intensity exercises could not improve the inhibitory effect of obesity on sex development.

[A preliminary study of serum marker alpha-enolase in the diagnosis of hepatocellular carcinoma].

Objective: To investigate the diagnostic value of serum α-enolase (ENO1) in the primary hepatocellular carcinoma. Methods: From May 2012 to March 2017, 163 cases with liver diseases who met the inclusion and exclusion criteria were admitted to the Infectious Diseases Department of the General Hospital of Ningxia Medical University. Among them, 28 cases were of chronic hepatitis B (CHB), 31 cases with liver cirrhosis (LC), 104 cases with hepatocellular carcinoma (HCC), and 18 healthy volunteers (NC). Patient data and serum samples were collected and liver disease related indicators were measured to detect ENO1 levels with enzyme-linked immunosorbent assay (ELISA). The measured indicators were expressed in median. Mann-Whitney U nonparametric test was used to analyze the differences between the data. A Spearman's correlation analysis was used for bivariate correlation analysis. The sensitivity and specificity of ENO1 and alpha-fetoprotein in the diagnosis of liver cancer were analyzed by ROC curve. Results: Serum level of ENO1 in CHB group, LC group and HCC group was significantly higher than normal group. Serum level of ENO1 in HCC group was higher than CHB group (P = 0.001) and LC group (P < 0.01). Area under the curve (AUC) for serum ENO1 and alpha-fetoprotein were 0.782 (cut-off value 75.96, P = 0.000 1) and 0.800 (cut-off value 27.02, P = 0.000 1), respectively. There was a positive correlation between ENO1 and AFP (P = 0.001). The combined detection had significantly improved the detection efficiency (AUC = 0.835). Serum ENO1 was statistically significant (P < 0.05) in HCC tumor size (AUC = 0.663), tumor metastasis (AUC = 0.681), TNM stage (AUC = 0.710, stage I vs. II), and Edmondson grade (AUC = 0.685) (P < 0.05) and the elevated levels of ENO1 had significantly reduced (P < 0.05) the survival time. Conclusion: ENO1 can be a new candidate marker for the diagnosis of early stage HCC and its progression.

[Paracondylar-lateral cervical approach for resection of jugular foramen schwannomas: a retrospective analysis of 15 cases].

Objective: To explore the effects of paracondylar-lateral cervical approach for resection of the jugular foramen schwannoma(JFS). Methods: A total of 15 patients with JFS operated via the paracondylar-lateral cervical approach between December 2011 and March 2016 at Department of Neurosurgery in Xiangya Hospital of Central South University were retrospectively analyzed. There were 7 males and 8 females, aging from 22 to 77 years with a mean age of (41.9±15.8) years.There were 12 patients who accepted primary surgery, 3 patients who accepted secondary surgery. There were 10 patients with tinnitus or hearing loss, 8 patients with dysphagia, 9 patients with hoarseness, 7 patients with tongue hemiparesis, 8 patients with ataxia, 1 patient with Pyramidal signs, 2 patients with facial hypesthesia or pain, 1 patient with facial paresis. According to Samii JFS grading system, 2 patients were type B, 4 were type C and 9 were type D. All patients were followed-up through outpatient and telephone by MRI in 3, 9, 12 months postoperation. Results: Gross total removal of tumors were achieved in 14 patients and subtotal removal in 1 patient. Two patients had new hoarseness, 2 had new dysphagia and 3 had more serious dysphagia, 1 patient had more serious facial paresis after the operation. There were 2 patients with intracranial infection, 2 with pneumonia, 1 with subcutaneous effusion, 1 with cerebrospinal fluid rhinorrhea, 5 with gastric intubation during perioperative period. There were no death, intracranial hematoma and decreased hearing patients. All patients were followed up, the follow-up time were 3 to 33 months with a mean of (26.9±11.2) months. Till to the latest follow up, dysphagia improved in 2 cases, hoarseness and tongue hemiparesis improved in 3 cases, hearing loss and tinnitus improved in 9 cases, balance function improved in 7 cases, facial hypesthesia and pain improved in 2 cases, pyramidal signs disappeared in 1 case, facial nerve function improved to normal in 1 case. There was no recurrence and progressed case. Conclusion: Paracondylar-lateral cervical approach is an alternative approach for both intracranial and extracranial JFS.

Stripe rust resistance and dough quality of new wheat - Dasypyrum villosum translocation lines T1DL•1V#3S and T1DS•1V#3L and the location of HMW-GS genes.

The transfer of agronomically useful genes from wild wheat species into cultivated wheat is one of the most effective approaches to improvement of wheat varieties. To evaluate the transfer of genes from Dasypyrum villosum into Triticum aestivum, wheat quality and disease resistance was evaluated in two new translocation lines, T1DL•1V#3S and T1DS•1V#3L. We examined the levels of stripe rust resistance and dough quality in the two lines, and identified and located the stripe rust resistant genes and high molecular weight glutenin subunit (HMW-GS) genes Glu-V1 of D. villosum. Compared to the Chinese Spring (CS) variety, T1DL•1V#3S plants showed moderate resistance to moderate susceptibility to the stripe rust races CYR33 and Su11-4. However, T1DS•1V#3L plants showed high resistance or immunity to these stripe rusts. The genes for resistance to stripe rust were located on 1VL of D. villosum. In comparison to CS, the dough from T1DS•1V#3L had a significantly shorter developing time (1.45 min) and stable time (1.0 min), a higher weakness in gluten strength (208.5 FU), and a lower farinograph quality index (18). T1DL•1V#3S had a significantly longer developing time (4.2 min) and stable time (5.25 min), a lower weakness in gluten strength (53 FU) and a higher farinograph quality index (78.5). We also found that T1DS•1V#3L had reduced gluten strength and dough quality compared to CS, but T1DL•1V#3S had increased gluten strength and dough quality. The results of SDS-PAGE analysis indicated that Glu-V1 of D. villosum was located on short arm 1VS and long arm 1VL. These results prove that the new translocation lines, T1DS•1V#3L and T1DS•1V#3L, have valuable stripe rust resistance and dough quality traits that will be important for improving wheat quality and resistance in future wheat breeding programs.

Effects of the consumption of rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric Kaschin-Beck disease: an epidemiological intervention trial in the Qinghai Province.

OBJECTIVE: Based on the aetiological hypothesis of Kaschin-Beck disease (KBD), different interventions were adopted, and the preventive and therapeutic effects of interventions was observed and evaluated in this trial. DESIGN: A total of 358 children from seven villages of Qinghai Province in China were examined, and 280 children aged 6-11 years old were eligible for the trial. The children were divided into three groups that received either no intervention (n = 64), 150 kg/person of rice from non-KBD areas (n = 103) or 7 kg/family of selenium-iodine salt (n = 113) for 12 months. Data were collected and used to calculate the proportion of patients with X-ray lesions, the proportion of new patients and the metaphyseal repair rate. All indicators were analysed with Pearson chi-square or Fisher's exact tests. The registration number of this trial is ChiCTR-PNRC-12002309 (http://www.chictr.org). RESULTS: After interventions, the proportion of patients with X-ray lesions increased dramatically in the control group and decreased significantly in two intervention groups; significant differences were seen between the control group and two intervention groups (P < 0.05). Moreover, significant differences were observed in the proportions of new patients and the metaphyseal repair rates between the control group and two intervention groups (P < 0.05). Additionally, the proportion of new patients was lowest and the metaphyseal repair rate was highest in group B. CONCLUSIONS: The effects of eating rice from non-KBD areas and selenium supplementation on the prevention and treatment of paediatric KBD were notable, the consumption of rice might be the most effective and safest intervention and should be encouraged.

Identification of Malassezia species in the facial lesions of Chinese seborrhoeic dermatitis patients based on DNA sequencing.

The genus Malassezia is important in the aetiology of facial seborrhoeic dermatitis (FSD), which is the most common clinical type. The purpose of this study was to analyse the distribution of Malassezia species in the facial lesions of Chinese seborrhoeic dermatitis (SD) patients and healthy individuals. Sixty-four isolates of Malassezia were isolated from FSD patients and 60 isolates from healthy individuals. Sequence analysis of the internal transcribed spacer (ITS) region was used to identify the isolates. The most frequently identified Malassezia species associated with FSD was M. furfur (76.56%), followed by M. sympodialis (12.50%) and M. japonica (9.38%). The most frequently isolated species in healthy individuals were M. furfur (61.67%), followed by M. sympodialis (25.00%), M. japonica (6.67%), M. globosa (3.33%), and M. obtusa (3.33%). Overall, our study revealed that while M. furfur is the predominant Malassezia species in Chinese SD patients, there is no significant difference in the distribution of Malassezia species between Chinese SD patients and healthy individuals.

Prediction of disease-related microRNAs by incorporating functional similarity and common association information.

The identification of human disease-related microRNAs (miRNAs) is important for understanding the pathogenesis of diseases, but to do this experimentally is a costly and time-consuming process. Computational prediction of disease-related miRNA candidates is a valuable complement to experimental studies. It is essential to develop an effective prediction method to provide reliable candidates for subsequent biological experiments. In this study, we constructed a miRNA functional similarity network based on calculation of the functional similarity between each pair of miRNAs. Here, we present a new method (DismiPred) for predicting disease-related miRNA candidates based on the network. This method incorporates functional similarity and common association information to achieve an efficient prediction performance. DismiPred has been successfully shown to recover experimentally validated disease-related miRNAs for 12 common human diseases, with an F-measure ranging from 69.49 to 91.69%. Furthermore, a case study examining breast neoplasms showed that DismiPred could uncover novel disease-related miRNAs. DismiPred is useful for further experimental studies on the involvement of miRNAs in the pathogenesis of diseases.

Hematoporphyrine injection-based photodynamic therapy for Perianal Paget's disease: A case report.

Paget's disease of the perianal skin (PPD) is a rare form of extramammary Paget's disease, which can manifest as either a primary intraepithelial adnexal neoplasm or as a secondary condition resulting from the spread of an underlying colorectal lesion. Surgical resection is the primary treatment for PDD, but it poses risks to the aesthetic appearance and functional integrity of the anus. Moreover, its clinical application is limited, particularly in cases of lesions present in multiple skinfold areas, multiple and recurrent lesions, extensive lesion areas, or in elderly patients with poor health. Hematoporphyrin derivative photodynamic therapy (HpD-PDT) serves as an alternative treatment for patients who are not suitable candidates for surgery and for conditions characterized by extensive and discontinuous disease. Here, we present the case of a 70-year-old man with PPD, presenting perianal skin lesions extending beyond the dentate line into the anal canal. When considering HpD-PDT, it is essential to take into account the preservation of function, patient preferences, and potential adverse effects. Subsequent to HpD-PDT, the lesion was effectively eradicated, and anal function was preserved without any notable proliferative, atrophic scarring, or other side effects. Therefore, HpD-PDT proves to be an effective treatment for PPD, offering aesthetic improvement, minimal functional disruption, and a high level of tolerability.

[Expert consensus on the biobank development of oral genetic diseases and rare diseases and storage codes of related biological samples from craniofacial and oral region].

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

Toxoplasma gondii infection in pregnant women in China.

Toxoplasmosis, caused by the protozoan parasite Toxoplasma gondii, is one of the most common parasitic infections in humans. Primary infection in pregnant women can be transmitted to the fetus leading to miscarriage or congenital toxoplasmosis. Carefully designed nationwide seroprevalence surveys and case-control studies of risk factors conducted primarily in Europe and America, have shaped our view of the global status of maternal and congenital infection, directing approaches to disease prevention. However, despite encompassing 1 in 5 of the world's population, information is limited on the status of toxoplasmosis in China, partly due to the linguistic inaccessibility of the Chinese literature to the global scientific community. By selection and analysis of studies and data, reported within the last 2 decades in China, this review summarizes and renders accessible a large body of Chinese and other literature and aims to estimate the seroprevalence in Chinese pregnant women. It also reviews the prevalence trends, risk factors, and clinical manifestations. The key findings are (1) the majority of studies show that the overall seroprevalence in Chinese pregnant women is less than 10%, considerably lower than a recently published global analysis; and (2) the few available appropriate studies on maternal acute infection suggested an incidence of 0·3% which is broadly comparable to studies from other countries.

[Clinical characteristics and comprehensive treatment of patients with cleidocranial dysplasia].

Objective: To summarize the clinical characteristics of patients with cleidocranial dysplasia (CCD) and analyze their treatment methods. Methods: From January 2000 to December 2020, patients with CCD who completed comprehensive treatment in the Department of Orthodontics and the First Dental Clinic, School and Hospital of Stomatology, China Medical University were retrospectively analyzed. A total of 14 CCD patients [7 males and 7 females, aged (16.1±4.5) years] were collected. There were 153 impacted permanent teeth in this study. In addition to the teeth that needed to be extracted due to special conditions, 147 impacted teeth were pulled into the dentition using closed traction. Patients were divided into adolescent group (≥12 years and<18 years, 10 patients) and adult group (≥18 years, 4 patients). Failure rate of traction was compared between the two groups. Factors affecting the success rate of closed traction such as vertical position of teeth (high, middle and low) and horizontal position of the teeth (palatal, median and buccal) were analyzed. Results: The incidence of maxillary impacted teeth [69.3% (97/140)] was higher than that of mandibular impacted teeth [40% (56/140)]. The difference was statistically significant (χ2=24.22, P<0.001). The supernumerary teeth were mainly located in the premolar area 61.4% (21/44), and most of them were in the palatal region of the permanent teeth 95.5% (42/44). They were generally located at the same height or the occlusal side of the corresponding permanent teeth. The success rate of closed traction was 93.9% (138/147). The success rate in the adolescent group [98.2% (108/110)] was higher than that in the adult group [81.1% (30/37)], and the difference was significant (χ2=14.09, P<0.05). Failure after closed traction of 9 teeth was found totally, including 7 second premolars. The success rate of traction in impacted second premolars at different vertical (χ2=11.44, P<0.05) and horizontal (χ2=9.71, P<0.05) positions in alveolar bone was different significantlly. The success rates of the second premolars were high (15/16), middle (12/13), low (2/7), and lingual palatine (10/17), median (19/19), lip-buccal (0/0), respectively. Conclusions: The closed traction of impacted teeth in patients with CCD was effective, and the age was the main variable affecting the outcome. The success rate of traction in impacted second premolars located in low position vertically or in palatal position was low, which required close observation during treatment.

CLCU-Net: Cross-level connected U-shaped network with selective feature aggregation attention module for brain tumor segmentation.

BACKGROUND AND OBJECTIVE: Brain tumors are among the most deadly cancers worldwide. Due to the development of deep convolutional neural networks, many brain tumor segmentation methods help clinicians diagnose and operate. However, most of these methods insufficiently use multi-scale features, reducing their ability to extract brain tumors' features and details. To assist clinicians in the accurate automatic segmentation of brain tumors, we built a new deep learning network to make full use of multi-scale features for improving the performance of brain tumor segmentation. METHODS: We propose a novel cross-level connected U-shaped network (CLCU-Net) to connect different scales' features for fully utilizing multi-scale features. Besides, we propose a generic attention module (Segmented Attention Module, SAM) on the connections of different scale features for selectively aggregating features, which provides a more efficient connection of different scale features. Moreover, we employ deep supervision and spatial pyramid pooling (SSP) to improve the method's performance further. RESULTS: We evaluated our method on the BRATS 2018 dataset by five indexes and achieved excellent performance with a Dice Score of 88.5%, a Precision of 91.98%, a Recall of 85.62%, a Params of 36.34M and Inference Time of 8.89ms for the whole tumor, which outperformed six state-of-the-art methods. Moreover, the performed analysis of different attention modules' heatmaps proved that the attention module proposed in this study was more suitable for segmentation tasks than the other existing popular attention modules. CONCLUSION: Both the qualitative and quantitative experimental results indicate that our cross-level connected U-shaped network with selective feature aggregation attention module can achieve accurate brain tumor segmentation and is considered quite instrumental in clinical practice implementation.

Prunella vulgaris L protects glucocorticoids-induced osteogenesis inhibition in bone marrow mesenchymal stem cells through activating the Smad pathway.

OBJECTIVE: To elucidate the role of Prunella vulgaris L (PVL) in protecting glucocorticoids (GC)-induced osteogenesis inhibition, thereafter, protecting the deterioration of osteoporosis (OP). MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay was conducted to assess the influence of PVL treatment on MSCs viability. Osteogenesis in MSCs was induced by Dexamethasone (DEX) stimulation. Regulatory effects of PVL on osteogenesis-related gene expressions, ALP activity, and mineralization ability in DEX-induced MSCs were determined. At last, protein levels of p-Smad1/5/9 and total-Smad1/5/9 influenced by DEX and PVL were measured by Western blot. RESULTS: PVL treatment did not pose a time- or dose-dependent influence on MSCs viability. DEX induction in MSCs downregulated ALP, RUNX2, Bglap, and Osterix. ALP activity and mineralization in DEX-induced MSCs were suppressed. Downregulated osteogenesis-related genes decreased ALP activity and mineralization in MSCs undergoing DEX stimulation were partially reversed by PVL treatment. Moreover, the downregulated p-Smad1/5/9 level in DEX-induced MSCs was elevated by PVL treatment, while total-Smad1/5/9 was not affected. CONCLUSIONS: PVL alleviated GC-induced suppression in MSCs osteogenesis by activating the Smad pathway, thereafter, protecting the deterioration of OP.

[Epidemiological and molecular characteristics of human brucellosis in Qinghai province, 2005-2019].

Objective: To analyze the epidemiological and molecular characteristics of human brucellosis in Qinghai province from 2005 to 2019 and provide basic data for brucellosis prevention and control. Method: The data about human brucellosis in Qinghai from 2005 to 2019 were collected from the information system of China CDC to describe the spatial, population and time distributions of human brucellosis cases in Qinghai. The isolated strains were identified and typed with traditional methods, BCSP31-PCR, AMOS-PCR and multi-locus variablenumber tandem repeat (MLVA-16). Results: A total of 577 human brucellosis cases were reported in Qinghai from 2005 to 2019, the average prevalence rate was 0.07 per 100 000 person, there were statistic differences among different years. The disease occurred all the year around, but mainly during March-October. The 577 cases were distributed in 31 counties (cities/districts) from 6 autonomous prefectures (cities). The prevalence rats of five counties were high, i.e. Menyuan Hui autonomous county (22.88%, 132/577), Tianjun county (10.57%, 61/577)、Xining city (10.57%, 61/577), Henan Mongol Autonomous County (10.51%, 58/577) and Haiyan county (9.53%, 55/577). Age of the cases ranged from 8 years to 82 years, and the male to female ratio of the cases was 1.8∶1 (374/203). The prevalence rate in herdsman (47.83%, 276/577) was highest among different occupational populations. Ten isolates were all Brucella melitensis strains, belonging to biovar 3, and clustering analysis indicated that the 10 strains had 5 genotypes, in which 2 were distinct, the remaining 3 were same. MLVA-16 analysis indicated that the 10 strains had close relationship with 26 B. melitensis strains isolated in Qinghai previously. Conclusions: The prevalence of brucellosis increased in Qinghai in recent years, we should strengthen the population based brucellosis surveillance and reporting. MLVA-16 indicated the gene diversity of the Brucella strains, suggesting that MLVA-16 can be used for genetic diversity analysis and molecular epidemiology survey to improve brucellosis surveillance.

[Clinical research of extensive alveolar cleft treatment with computer assistant distraction osteogenesis].

Objective: To evaluate the feasibility and outcome of computer assisted distraction osteogenesis in the treatment of extensive alveolar cleft. Methods: Four patients [1 male and 3 females, aged (15.5±3.7) years] received treatment in the Department of Oral-Maxillofacial Surgery and Plastic Surgery, School of Stomatology, China Medical University from June 2016 to April 2018 were involved in this study. All the patients with extensive alveolar cleft [cleft width (7.64±1.29) mm] were performed orthodontic treatment to expand the dental arch and interdental space between the first molar and premolars. Three-dimensional (3D) model of the maxilla and the osteotomy guider were printed according to the CT data. The fix wings of the distractor were pre-shaped according to the 3D model. The osteotomy was performed at the interdental space and horizontal plate of palate to dissociate the alveolar bone segment. The distractor was fixed on the predetermined position. Distraction (0.4-0.8 mm/day) was performed in 7 days later and stopped when the incision connected with the canine. The distractor was removed after six months. Results: The distraction period was (10.8±2.5) d in four cases. The cleft was completely closed with interdental bone anchored distraction in four cases. The imaging examination in six months showed good new bone structure in the distraction zone and bone connection of the cleft. Conclusions: Computer assisted distraction osteogenesis was effective and feasible to close the extensive alveolar cleft and provide sufficient new bone tissue.

Concerted activity of tyrosine phosphatase SHP-2 and focal adhesion kinase in regulation of cell motility.

The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the adhesion of MCF-7 to vitronectin and collagen in a dose- and time-dependent manner, suggesting that IGF-I triggers the activation of different integrins. On the other hand, IGF-I promotes the association of insulin receptor substrate 1 with the focal adhesion kinase (FAK), paxillin, and the tyrosine phosphatase SHP-2, resulting in FAK and paxillin dephosphorylation. Abrogation of SHP-2 catalytic activity with a dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced FAK dephosphorylation, and cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared with either mock- or SHP-2 wild-type-transfected cells. This impairment of cell migration is recovered by reintroduction of a catalytically active SHP-2. Interestingly, SHP-2-C>S cells show a larger number of focal adhesion contacts than wild-type cells, suggesting that SHP-2 activity participates in the integrin deactivation process. Although SHP-2 regulates mitogen-activated protein kinase activity, the mitogen-activated protein kinase kinase inhibitor PD-98059 has only a marginal effect on MCF-7 cell migration. The role of SHP-2 as a general regulator of cell chemotaxis induced by other chemotactic agents and integrins is discussed.

Identification of an orally available compound with potent and broad FLT3 inhibition activity.

FLT3 internal tandem duplication (FLT3-ITD) is an activating mutation found in 20-30% of patients with acute myeloid leukemia (AML), which makes FLT3 an attractive target for the treatment of AML. Although FLT3-mutant patients respond to current FLT3 inhibitors, relapse usually happens because of the acquisition of resistant secondary mutations at the FLT3 catalytic domain, which is mainly on D835. In the search for compounds with broad FLT3 inhibition activities, we screened a kinase inhibitor library by using our unique FLT3 substrate and identified JAK3 inhibitor VI (designated JI6 hereafter) as a novel FLT3 inhibitor, which selectively targets FLT3 D835 mutants as well as FLT3-ITD. JI6 effectively inhibited FLT3-ITD-containing MV4-11 cells and HCD-57 cells transformed with FLT3-ITD and D835 mutants. Furthermore, administration of JI6 effectively targeted FLT3 signaling in vivo and suppressed the myeloproliferative phenotypes in FLT3-ITD knock-in mice, and significantly prolonged the survival of immunodeficient mice implanted with the transformed HCD-57 cells. Therefore, JI6 is a promising candidate for the development of next-generation anti-AML drugs.