[Injury mechanism, clinical status and prospects of traumatic brain injury].

Traumatic brain injury (TBI) is an important in the world's public health and an important subject of basic and clinical research in the medical field. In the past 30 years, the epidemiology, injury mechanism, safety prevention, medical strategies, nursing measures and other aspects of TBI have made great progress, and the level of treatment has also been continuously improved, but it still faces many challenges. The focus of research on the injury mechanism of TBI has gradually shifted from the classic signaling pathways of primary injury to the study of secondary injury mechanisms. Pharmacological research on various therapeutic targets has also made significant progress, which is expected to be transformed into new TBI therapeutic drugs. On the other hand, many new clinical concepts, new systems, and new methods are constantly being integrated into the diagnosis and treatment of TBI, which has gradually transformed from the original treatment of acute neurological injury to the comprehensive treatment of chronic systemic diseases. This paper is based on the latest research progress in the basic and clinical aspects of TBI, and provides a review of its current status and development trends, providing reference for the medical treatment and research of TBI.

Blood transcriptome analysis and identification of genes associated with supernumerary teats in Chinese Holstein cows.

In dairy cows, supernumerary teats (SNT) are not desired as they are considered a repository for bacteria; thus, SNT are a risk factor for mastitis. Supernumerary teats are a heritable oligo- or polygenic trait. The incidence of SNT in offspring must be reduced by genomic selection. However, in modern dairy farming, farmers often ignore the effects of SNT on cows. The study aimed to elucidate the effects of SNT on dairy cows from the blood transcriptome level and identify genes associated with SNT in Chinese Holstein cows. We selected 6 SNT cows (Yes) and 6 non-SNT cows (No). In the 6 SNT cows, 3 cows had 1 SNT (One) and 3 cows had 2 SNT (Two). They were divided into 3 comparison groups (One vs. No; Two vs. No; and Yes vs. No). RNA was extracted from blood white membrane cells of 12 cows, and RNA sequencing was performed. Differential gene expression analysis based on the negative binomial distribution was used to detect differentially expressed genes in the One versus No and Two versus No comparison groups. Genes that were significantly upregulated or downregulated both in the One versus No and Two versus No groups (shared genes, SG) were obtained for further analysis. We also performed gene set enrichment analysis for all genes expressed in the Yes versus No group, correlation analysis between SG and the hematological parameters, protein-protein interaction network analysis of SG to select hub genes, and alternative splicing analysis for Yes versus No group to explore the functions of differentially spliced genes. We detected 289 SG. Gene set enrichment analysis, gene ontology, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis results showed that SNT affect immunity, inflammation, and lactation-related pathways in dairy cows. Correlation analysis showed that LOC104968484, SLC25A6, GADD45G, BAX, APAF1, ATM, XIAP, MDM4, BDP1, CEP350, MED13, TAOK1, SMG1, and RIF1 are associated with white blood cell count and absolute value of lymphocytes in SNT cows only, so they might be genes associated with SNT in Chinese Holstein cows. We found 2 genes (BAX and MDM4) were also differentially spliced genes. However, the causal relationship between these genes and the SNT phenotype needs to be further studied. This study is the first to reveal the adverse effects of SNT on dairy cows at a transcriptional level, and the genes we found can be used as a reference for further searching for candidate genes for the SNT phenotype.

High-Efficiency Arbitrary Quantum Operation on a High-Dimensional Quantum System.

The ability to manipulate quantum systems lies at the heart of the development of quantum technology. The ultimate goal of quantum control is to realize arbitrary quantum operations (AQUOs) for all possible open quantum system dynamics. However, the demanding extra physical resources impose great obstacles. Here, we experimentally demonstrate a universal approach of AQUO on a photonic qudit with the minimum physical resource of a two-level ancilla and a log_{2}d-scale circuit depth for a d-dimensional system. The AQUO is then applied in a quantum trajectory simulation for quantum subspace stabilization and quantum Zeno dynamics, as well as incoherent manipulation and generalized measurements of the qudit. Therefore, the demonstrated AQUO for complete quantum control would play an indispensable role in quantum information science.

[Effect of exogenous gonadotropin dosage on embryo aneuploidy rate and pregnancy outcome in patients of preimplantation genetic test].

Objective: To investigate the effect of gonadotropin (Gn) on embryo aneuploidy rate and pregnancy outcome during preimplanptation genetic testing for aneuploidy (PGT-A) cycles. Methods: The clinical data of patients undergoing PGT-A cycle at the First Medical Center of the PLA General Hospital from January 1, 2013 to May 31, 2019 were retrospectively analyzed. Patients were divided into younger patient group (<35 years old) and elder patient group (≥35 years old) by maternal age, then divided into two groups in line with Gn dosage (≤2 250 U, >2 250 U), and into four groups by number of oocytes retrieved (1-5, 6-10, 11-15 and ≥16 oocytes). The embryo aneuploidy rate and pregnancy outcome between the groups were compared. Logistic regression was used to analyze the relationship between the cumulative amount of Gn, embryo aneuploidy rate and live-birth rate. Results: A total of 402 cycles (338 patients) and 1 883 embryos were included in the study. (1) In the younger patients, the aneuploidy rate was 52.5% (304/579) in the group of Gn≤2 250 U and 48.6% (188/387) in the group of Gn>2 250 U, with no significant difference between them (P=0.232). In the elderly patients, the difference in embryo aneuploidy rate between the two Gn group [57.9% (208/359) versus 60.6% (319/526)] was not statistically significant (P=0.420). (2) The embryonic aneuploidy rate in different protocol of ovary stimulation was analyzed,in the younger group, the embryonic aneuploidy rate in patients using antagonist long protocol was 50.3% (158/314), it was 50.0% (121/242) in agonist long protocol, 52.1% (207/397) in agonist short protocol and 6/13 in luteal phase protocol, no statistical difference was found in above groups (P=0.923); in the elder group, embryonic aneuploidy rate was 60.8% (191/314) in antagonist protocol, 58.4% (132/226) in agonist long protocol, 59.2%(199/336) in agonist short protocol, 5/9 in luteal phase protocol, respectively,no significant difference was found (P=0.938). (3) In the younger patients, the aneuploidy rate in 1-5 oocytes group, 6-10 oocytes group, 11-15 oocytes group and ≥16 oocytes group was 37.9% (11/29), 54.0% (94/174), 52.5% (104/198) and 50.1% (283/565) respectively, no significant difference was found between the groups (P=0.652); while in the elder patients, the difference between aneuploidy rate in each retrieved oocytes group [73.6% (89/121), 57.5% (119/207), 56.3% (108/192), 57.8% (211/365)] was statistically significant (P=0.046). (4) Logistic regression analysis of age, cumulative dosage of Gn, number of oocytes obtained, and embryo aneuploidy rate showed that there was no association between the amount of Gn and embryo aneuploidy rate (P>0.05); the increase in maternal age would increase the risk of aneuploidy rate of embryos, which was statistically significant (OR=1.031, 95%CI: 1.010-1.054, P=0.004); the increase in oocytes retrived would significantly decrease the risk of aneuploidy (OR=0.981, 95%CI: 0.971-0.991, P<0.01). (5) There was no significant difference in biochemical pregnancy rate [55.6% (80/144) versus 52.1% (63/121)], clinical pregnancy rate [50.0% (72/144) versus 47.9% (58/121)] and live-birth rate [46.5% (67/144) versus 40.5% (49/121)] between different Gn dosage groups (P=0.613, P=0.738, P=0.324). The logistic regression analysis showed that the maternal age, the cumulative dosage of Gn, the number of oocytes obtained, and the ovarian stimulation protocol had no effect on the live-birth rate (all P>0.05). Conclusions: In PGT-A cycle, the dosage of Gn has no association with the embryo aneuploidy rate and pregnancy outcome. In the patients ≥35 years old, the increase in number of oocytes obtained may decrease the risk of aneuploidy. Age is an important factor affecting the embryo aneuploidy in PGT-A cycle.

[Safety analysis of 12 241 infants inoculated in three sites of diphtheria, tetanus, acellular pertussis and haemophilus influenzae type b combined vaccine in Chaoyang District of Beijing].

Objective: To observe the adverse reactions of Diphtheria, Tetanus, Acellular Pertussis and Haemophilus Influenzae Type b Combined Vaccine conjugate vaccine at the anterolateral thigh muscle, upper arm deltoid muscle and upper gluteal region. Methods: A total of 12 241 infants who were voluntarily vaccinated DTaP-Hib from April 2015 to April 2019 in Beijing were selected for the study. DTaP-Hib vaccine is recommended for 3, 4, 5 months of age for basic immunization and 18 to 24 months of age to strengthen immunization. Subjects were divided into the groups of lateral thigh muscle, the upper arm deltoid and upper gluteal region according to the actual inoculation sites. Adverse reactions were collected within 30 minutes and 7 days after each does of vaccination at different sites and compared between three groups. The incidence of adverse reactions at the three different inoculation sites was compared by Chi-square test. Results: A total of 12 241 infants and toddlers received combined DTaP-Hib and 35 027 doses of DTaP-Hib were investigated. The number and of lateral thigh muscles, upper arm deltoids and gluteal muscles were 3 461 infants and 11 129 doses, 2 659 infants and 7 957 doses, 6 121 infants and 15 941 doses respectively. A total of 2 489 adverse reactions occurred. The incidence of adverse reactions was 7.11%. The incidence of adverse reactions in deltoid muscle of upper arm was 9.69%（771 doses）, which was higher than that in gluteal muscle (7.58%, 1 211 doses) and anterolateral muscle of thigh (4.56%, 507 doses). The incidence of mild, moderate and severe adverse reactions in the upper arm deltoid group were higher than those in the other two groups. The incidence rates were 4.85% (386 doses), 3.77% (300 doses) and 1.07% (85 doses) respectively. The differences between groups were statistically significant（P<0.001）. The total adverse reactions of the three doses of basic immunization and the fourth dose of enhanced immunization had the same trend in different parts. The incidence of adverse reactions was in the order of the upper arm deltoid injection, upper gluteal injection and lateral thigh muscle injection from high to low. The differences were statistically significant (P<0.001). Conclusion: The incidence of adverse reactions of DTaP-Hib vaccination in three different sites was low, which confirmed that the DTaP-Hib vaccination got expected safety regardless of the sites of inoculation. The lateral femoral muscle group had the lowest incidence of adverse reactions, hence it should be preferred as the inoculation site of DTaP-Hib vaccination.

[Analysis of single-nucleotide polymorphism of Sonic hedgehog signaling pathway in non-syndromic cleft lip and/or palate in the Chinese population].

OBJECTIVE: To study the relationship between Sonic hedgehog (Shh) associated single-nucleotide polymorphism (SNP) and non-syndromic cleft lip and/or palate (NSCL/P), and to explore the risk factors of cleft lip and/or palate. Many studies suggest that the pathogenesis of NSCL/P could be related to genes that control early development, in which the Shh signaling pathway plays an important role. METHODS: Peripheral blood was collected from 197 individuals (100 patients with NSCL/P and 97 healthy controls). Haploview software was used for haplotype analysis and Tag SNP were selected, based on the population data of Han Chinese in Beijing of the international human genome haplotype mapping project. A total of 27 SNP were selected for the 4 candidate genes of SHH, PTCH1, SMO and GLI2 in the Shh signaling pathway. The genotypes of 27 SNP were detected and analyzed by Sequenom mass spectrometry. The data were analyzed by chi-squared test and an unconditional Logistic regression model. RESULTS: The selected SNP basically covered the potential functional SNP of the target genes, and its minimum allele frequency (MAF) was >0.05: GLI2 73.5%, PTCH1 91.0%, SMO 100.0%, and SHH 75.0%. It was found that the genotype frequency of SNP (rs12674259) located in SMO gene and SNP (rs2066836) located in PTCH1 gene were significantly different between the NSCL/P group and the control group. Linkage disequilibrium was also found on 3 chromosomes (chromosomes 2, 7 and 9) where the 4 candidate genes were located. However, in the analysis of linkage imbalance haplotype, there was no significant difference between the disease group and the control group. CONCLUSION: In China, NSCL/P is the most common congenital disease in orofacial region. However, as it is a multigenic disease and could be affected by multiple factors, such as the external environment, the etiology of NSCL/P has not been clearly defined. This study indicates that Shh signaling pathway is involved in the occurrence of NSCL/P, and some special SNP of key genes in this pathway are related to cleft lip and/or palate, which provides a new direction for the etiology research of NSCL/P and may provide help for the early screening and risk prediction of NSCL/P.

[Clipping for large paraclinoid internal carotid artery aneurysms by non-fluoroscopic occlusion via a micro-bone window frontolateral approach].

Objective: To evaluate the clinical value and outcomes of technical improvement of hybrid operatical clipping for large paraclinoid internal carotid artery aneurysms. Methods: A review was conducted on 18 cases of large paraclinoid internal carotid artery aneurysm which were clipped by balloon non-fluoroscopic occlusion of the parent artery via a micro-bone window frontolateral approach in hybrid operating room at Neurosurgery Department of Tianjin Medical University General Hospital from June 2014 to December 2017. There were 8 males and 10 females with age of (63±4) years. There were 6 cases of unruptured aneurysm and 12 cases of ruptured aneurysm of subarachnoid hemorrhage (6 cases of grade Ⅱ, 4 cases of grade Ⅲ and 2 cases of grade Ⅳ in Hunt-Hess classification). Frontolateral approach incision (average length of about 5 cm) and bone window about 3 cm×3 cm were performed. No incision of the neck was needed to expose the internal carotid artery for temporary occlusion. In the operation, the balloon was slowly pushed to the preset position of the internal carotid artery under non-fluoroscopy. The balloon was expanded to block the blood flow of internal carotid artery. Then aneurysm was clipped. The balloon was loosened and retraced to the guiding catheter after clipping. The clipping condition was examined by cerebral angiography. If there was residual aneurysm neck or stenosis of the parent artery, the balloon was pushed under non-fluoroscopy again to temporary occlusion and the clip was adjusted until the aneurysm neck was clamped satisfactorily. Results: Eighteen aneurysms were successfully clipped in hybrid operating room. Fourteen aneurysms showed complete occlusion of the aneurysm neck and no stenosis of the parent artery. Four cases showed residual aneurysm neck after clipping by intraoperative angiography, then aneurysms were clipped satisfy by adjusting the aneurysm clip. The patients were followed up for 3 months to 1 year. Ten patients recovered well (modifed Rankin score (mRS): 0), and 3 patients had no obvious disability (mRS: 1). Two patients with Hunt-Hess grade Ⅲ were slightly disabled (mRS: 2). 1 patients with Hunt-Hess grade Ⅲ were moderately disabled (mRS: 3). 1 patients with Hunt-Hess grade Ⅳ were severely disabled (mRS: 4). One elderly patients with Hunt-Hess grade Ⅳ were seriously disabled (mRS: 5). Conclusions: Application of balloon non-fluoroscopic occlusion clipping for large paraclinoid internal carotid artery aneurysm via a micro-bone window frontolateral approach is safe, effective and minimally invasive.

[Application of hybrid operating room in the treatment of spinal dural arteriovenous fistulas].

Objective: To explore the experience in the treatment of spinal dural arteriovenous fistulas with application of hybrid operating room. Method: A retrospective analysis was performed among 22 patients with spinal dural arteriovenous fistulas admitted to Department of Neurosurgery of Tianjin Medical University General Hospital who received operation in the hybrid operating room from March 2011 to February 2016. Modified Aminoff-Logue scores (ALS) for myelopathy was used to evaluate the spinal function.All the 22 patients were followed up 6-12 months after the operation. Result: All the patients were diagnosed by spinal digital subtraction angiography (DSA). The modified ALS pre-operation and post-operation 6 months were (4.7±1.8) and (2.0±1.5), respectively, with significant difference (P<0.01). There were 15 cases with mild dysfunction, 6 cases with moderate dysfunction, severe dysfunction in 1 case before operation.Fifteen cases were cured, 4 cases improved, 1 case had no change after 6 months follow-up.The improvement rate was 95.45%. Conclusion: The application of hybrid operating room in the treatment of spinal dural arteriovenous fistulas achieves good outcome and provides a convenient and effective approach, which embodies the idea of precision medicine.

[Clinical experience of 302 cases with brain abscess].

Objective: To compare the diagnosis and treatment experience of brain abscesses and improve prognosis. Methods: The data of 302 patients of brain abscess at Department of Neurosurgery in Tianjin Medical University General Hospital from 1980 to 2014 was analyzed retrospectively. There were 215 male and 87 female patients aged from 11 to 82 years with mean age of (30±8) years. The patients was divided into 1980-2001 group and 2002-2014 group according to different diagnosis and the treatment methods. The therapy methods include operation and conservative treatment. There were 196 cases received operation, including 95 cases of excision, 89 cases of ventriculopuncture, 12 cases of excision after ventriculopuncture, 106 cases received drug conservative therapy. Two groups of information including clinical manifestation, abscess location, therapeutic effect and prognosis were compared by χ(2) test. Results: Compared to 1980-2001 group, adjacent infection incidence declined(χ(2)=8.000, P=0.005). The ratio of single abscess declined and multiple abscess increased(χ(2)=11.060, P=0.001), the infection proportion of frontal lobe and temporal lobe decreased(χ(2)=9.080, P=0.003; χ(2)=15.440, P=0.000). The ratio of headache and vomit and papilledema declined significantly(χ(2)=23.290, P=0.000; χ(2)=21.020, P=0.000; χ(2)=2.290, P=0.001). Total mortality of 302 patients were 23 cases and 5 cases of 1980-2001 group and 2002-2014 group (10.4% vs. 6.3%, χ(2)=1.180, P=0.277). However, there were statistical difference in postoperative mortality between both groups (14.4% vs. 4.0%, χ(2) =3.880, P=0.049). Conclusion: With the application of antibiotics and the development of neurosurgical techniques, the prognosis of brain abscess has been improved.

Brain functional connectivity and cognition in mild traumatic brain injury.

INTRODUCTION: The aim of this study was to analyze brain functional connectivity and its relationship to cognition in patients with mild traumatic brain injury (mTBI). METHODS: Twenty-five patients with mTBI and 25 healthy control subjects were studied using resting-state functional MRI (rs-fMRI). Amplitudes of low-frequency fluctuations (ALFFs) and functional connectivity (FC) were calculated and correlated with cognition. RESULTS: Compared with the normal control group, the mTBI patients showed a significant decrease in working memory index (WMI) and processing speed index (PSI), as well as significantly decreased ALFFs in the cingulate gyrus, the middle frontal gyrus and superior frontal gyrus. In contrast, the mTBI patients' ALFFs in the left middle occipital gyrus, the left precuneus, and lingual gyrus increased. Additionally, FC significantly decreased in the thalamus, caudate nucleus, and right hippocampus in the mTBI patients. Statistical analysis further showed a significant positive correlation between the ALFF in the cingulate gyrus and the WMI (R (2) = 0.423, P < 0.05) and a significant positive correlation between the FC in the left thalamus and left middle frontal gyrus and the WMI (R (2) = 0.381, P < 0.05). CONCLUSION: rs-fMRI can reveal the functional state of the brain in patients with mTBI. This finding differed from observations of the normal control group and was significantly associated with clinical cognitive dysfunction. Therefore, rs-fMRI offers an objective imaging modality for treatment planning and prognosis assessment in patients with mTBI.

[Study on the difference of blood coagulation function in patients with traumatic brain injury in plain and plateau area].

Objective: In this study, we tested platelet count (PC), prothrombin time (PT), activated partial thromboplastin time (APTT), and other indicators of coagulation function, and revealed their difference in patients with traumatic brain injury (TBI) between plain and plateau area. Base on the results, we may provide research basis for the therapy of TBI associated coagulopathy in different areas. Methods: 151 TBI patients from Tianjin Medical University General Hospital, and 74 from People's Hospital of Tibet Autonomous Region in the period from Dec 2013 to Dec 2015 were enrolled.Coagulation function, including PC, platelet distribution width (PDW), mean platelet volume (MPV), platelet - large cell ratio (P- LCR), PT, APTT, fibrinogen (FIB), and D- Dimer were tested within 8 h. The difference in patients with TBI between plain and plateau areas were compared and analyzed. Results: Compared with plain area, the PC of patients with TBI in plateau area is lower [(168±49)×109/L vs (196±72)×109/L, P<0.05], while PT and APTT were extended [(13.5±1.3) s vs (12.0±4.0) s, (38±4) s vs(27±6) s, P<0.01]. On the other hand, FIB increases [(3.1±1.2) g/L vs (2.6±1.0) g/L, P<0.01] and D-Dimer decreases [(3.1±3.3) µg/L vs (4.7±3.6) µg/L, P<0.01] in plateau area compared with plain area. Conclusion: Due to the people of plateau area living in hypoxia state, the coagulation function is activated for a long time.Once TBI happens, the platelets and coagulation factors may be excessive consumption, resulting in hypocoagulable state and high risk of rebleeding, while the fibrinolysis system in patients with TBI of plateau area is not activated obviously.Therefore, it should give full consideration to these differences in the treatment of patients with TBI in plateau area, instead of directly copying the standard therapy of the people in plain area.The treatment recommendations should primarily supplement coagulation materials, and antifibrinolytics may unlikely have the therapy effect.

[Stereotactic brain biopsy guided by iMRI co-registration combined with PET/CT].

OBJECTIVE: To explore the clinical value of intraoperative magnetic resonance imaging (iMRI) coregistration combined with position emission tomography/computed tomography (PET/CT) in stereotactic brain biopsy. METHODS: Forty nine patients with intracranial lesions were operated by stereotactic biopsy from June 2010 to June 2015 in Tianjin Medical University General Hospital. Seventeen patient's operation was guided by iMRI only (group A), thirty two patients' operation was guided by iMRI and PET/CT (group B). The diagnosis success rate and operation related complications were compared between the two groups. RESULTS: PET/CT and iMRI were integrated successfully in all cases of group B. Fourteen patients (82.4%) of group A and all 32 patients (100%) of group B had final diagnosis confirmed by histopathological and immunohistochemical observation. The diagnosis success rate of group B was higher than group A (P<0.05). There were 5 patients in total who had postoperative complication, 2 (11.8%) in group A and 3 (9.3%) in group B, but the difference was not statistically significant. CONCLUSIONS: PET/CT based metabolic imaging can be automatically integrated with standard MRI guided stereotactic biopsy. Compared with iMRI only, the combined treatment improves diagnosis success rate without increasing complications; it's safe, and has high clinical efficacy.

[Comparative study on the HIV epidemic between the Chinese and Burmese drug users in drug rehabilitation places in Dehong Prefecture, Yunnan Province].

Objective: To compare the prevalence of HIV infection and its risk factors among Chinese and Burmese drug users living in Dehong Prefecture, Yunnan Province. Methods: We obtained plasma specimens and gathered demographic data from 7 867 drug users with Chinese or Burmese nationality attending rehabilitation clinics in Dehong Prefecture from October 2014 to September 2015. Of these, 7 756 individuals who gave valid questionnaire responses, including 5 389 Chinese and 2 367 Burmese, were enrolled in the study after giving informed consent. We used the Chi-squared test to compare the demographic characteristics and HIV prevalence between the Chinese and Burmese drug users. Logistic regression was then used to identify risk factors for HIV infection. Results: The HIV infection rate of 7 756 subjects (aged (35.45 ± 10.91) years old) was 7.18%, in which Burmese with higher HIV infection rate (9.38%, 222/2 367) than Chinese (6.22%, 335/5 389) (χ2=24.21, P<0.001). In chinese drug users, OR (95%CI) of HIV infection of those aged 25-34 years old, 35-44 years old and ≥45 years old were 2.88 (1.46-5.69), 5.72 (2.87-11.40) and 3.48 (1.66-7.27),compared with those aged below 25 years;Compared with married participants, OR (95% CI) of those unmarried and divorced were 1.44 (1.08-1.93) and 1.56 (1.09-2.24); Jingpo drug users were 1.47 (1.07-2.04) times to get HIV infection,compared with Han ethnicity; OR (95%CI) of HIV infection for IDUs was 11.48 (9.73-16.01) compared with NIDUs.In Burmese drug users, OR (95% CI) of HIV infection for females was 0.50 (0.26-0.93) compared with men;Compared with those aged below 25 years,those aged 25-34,35-44 and ≥45 years had OR (95% CI) of 1.82 (1.18-2.77), 2.90 (1.82-4.62) and 2.31 (1.24-4.30), respectively; OR (95% CI) of Jingpo participants was 2.22 (1.44-3.41) compared with Han nationality; OR (95%CI) of HIV infection for IDUs was 10.61 (7.68-14.64) compared with NIDUs. Conclusion: The HIV infection rate of Burmese drug users was higher than that of Chinese drug users. Measures of HIV prevention and control should be mainly allocated in those 25 years above, non-married, Jingpo ethnicity and IDU in Chinese drug users, while in Burmese drug users,those females, 25 years above, Jingpo ethnicity and IDU should be higlighted in HIV prevention and control.

[Comparison of genotypes of hepatitis C virus between Chinese and Burmese drug users living in Dehong Prefecture, Yunnan Province].

Objective: To analyze the distribution of hepatitis C virus (HCV) genotypes among Chinese and Burmese drug users in Dehong Prefecture, Yunnan Province. Methods: Plasma specimens and relevant epidemiological data were collected from 7 545 drug users attending rehabilitation centers and methadone clinics in Dehong Prefecture from January to September in 2015, of which 752 were positive for HCV antibodies. HCV RNA was then extracted from 139 random specimens (64 Burmese and 75 Chinese) and the CE1 and NS5B regions were amplified by nested PCR. The sequences of these HCV genes were aligned, a phylogenetic tree was constructed using MEGA 6.0.6 and the average genetic discrete rate of each subtype group was calculated. We used Fisher's exact test to compare distribution of HCV subtypes from different people, using analysis of variance to compare the discrete rates of different CE1 and NS5B subtypes. Results: While we successfully amplified RNA from 43 specimens provided by Burmese patients (67%), including 31 with CE1 region and 38 with NS5B region, 52 from Chinese patients (69%) were successfully amplified including 43 with CE1 region and 45 with NS5B region. We found that 3b and 6n were the predominant subtypes and were found in 27% (n=14) and 37% (n=19) of Chinese and 28% (n=12) and 33%(n=14) of Burmese specimens. Subtypes 6u, 3a, 1a and 1b were present in 14%(n=7), 19%(n=10), 2% (n=1) and 2%(n=1) of Chinese specimens and 16%(n=7), 5%(n=2), 16%(n=7) and 2%(n=1) of Burmese specimens respectively. While the prevalence of subtype 1a was higher among samples from Burmese patients than Chinese patients (P=0.015), the presence of subtype 3a was higher among the latter (P=0.031). The discrete rates of CE1 region subtypes 1a, 1b, 3a, 3b, 6n and 6u were 0.048±0.007, 0.091±0.013, 0.074± 0.008, 0.061 ± 0.006, 0.136 ± 0.009 and 0.031 ± 0.005 (F=516.26, P<0.001). The discrete rates for NS5B region subtypes 1a, 1b, 3a, 3b, 6n and 6u, meanwhile, were 0.032±0.006, 0.065±0.012, 0.058±0.008, 0.041± 0.005, 0.059 ± 0.008, 0.045 ± 0.006 (F=45.11, P<0.001). Conclusion: Six HCV subtypes were identified among drug users in Dehong Prefecture, of which 6n and 3b were predominant. There were statistically significant differences in the distribution of subtypes 1a and 3b, which have been circulating for a long time in this population, between samples from Chinese and Burmese participants.

[Tracing hepatitis C virus transmission by using high-throughput sequencing technique].

OBJECTIVE: An approach for analysis of hepatitis C virus (HCV) quasispecies using Hiseq high-throughput sequencing (hereinafter referred to as Hiseq sequencing) technique was developed and then applied to investigate a possible case of HCV needle sharing transmission. METHODS: One case of HCV antibody seroconversion (P1) was found in a methadone clinic on January 15, 2015. Four HCV antibody positive injecting drug users (IDUs), P2 to P5, suspected to be involved in needle sharing transmission with P1 during the period (after March 24, 2014) that P1 may be infected with HCV were investigated, and another 28 HCV antibody positive IDUs were selected as controls (C1 to C28). These controls came from the same methadone clinic or lived in the same town with P1. The RNAs were extracted from the plasma specimens and then reverse-transcribed into cDNA. After HCV subtyping, Hiseq sequencing was performed to detect and sequence the HCV quasispecies (263 bp) in the specimens with the same subtype as P1. The frequency of quasispecies was counted and ranked. Intrapersonal and interpersonal genetic distance and phylogenetic tree were calculated. RESULTS: The HCV subtype of specimen P1 was 3b. All the other specimens with the same subtype were P2, C7, C12, C14, C15, C16, C19, C20 and C28. Hiseq sequencing was successfully performed in 9 out of these 10 specimens, and 249 753 to 1 086 333 (average 869 608) cleaned sequences representing 3 to 172 (average 48) unique HCV quasispecies were obtained. The medians (P50) of intrapersonal genetic diversities from the 9 specimens were 0.4% to 12.3%. The P50 (P25, P75) of genetic diversities between P1 and the other 8 specimens were 19.0% (18.4%, 19.8%), 10.4% (2.8%, 18.3%), 19.6% (17.8%, 21.4%),24.9% (23.8%, 26.1%), 19.8% (18.7%, 20.7%), 20.1% (18.9%, 21.2%), 20.6% (20.0%, 21.1%), 23.6% (22.4%, 24.8%). There were no significant difference between the genetic diversities of P1 and P2 and those of P1 and other 7 specimens (H=9.40, P=0.100). The genetic diversities between few HCV quasispecies from P1 and few ones from C7 were 0. Phylogenetic tree analysis indicated that there was no HCV transmission relationship between P1 and P2, but there was HCV transmission relationship between P1 and C7. CONCLUSION: With the feature of high-throughput, easier operation and lower cost, Hiseq sequencing technique has high practical value in tracing HCV transmission at the quasispecies level.

Lenalidomide affect expression level of cereblon protein in multiple myeloma cell line RPMI8226.

We investigated the mechanisms of action of immuno-modulatory drug (lenalidomide) on the protein expression of cereblon (CRBN) and their therapeutic targets in the multiple myeloma cell line RPMI8226. The multiple myeloma cell line RPMI8226 was cultured and treated with different concentrations of lenalidomide and bortezomib to determine the proliferation inhibition rate, apoptosis rate, and protein expression of CRBN. The results revealed that both lenalidomide and bortezomib inhibited the proliferation of RPMI8226 and promoted cell apoptosis. However, the protein expression of CRBN decreased signifi-cantly after treatment with lenalidomide, while bortezomib had no effect on the expression of CRBN. We confirmed that CRBN may be a target of lenalidomide.

Intracranial aneurysm risk factor genes: relationship with intracranial aneurysm risk in a Chinese Han population.

Few studies have examined the genes related to risk fac-tors that may contribute to intracranial aneurysms (IAs). This study in Chinese patients aimed to explore the relationship between IA and 28 gene loci, proven to be associated with risk factors for IA. We recruited 119 patients with aneurysms and 257 controls. Single factor and logistic regression models were used to analyze the association of IA and IA rup-ture with risk factors. Twenty-eight single nucleotide polymorphisms (SNPs) in 22 genes were genotyped for the patient and control groups. SNP genotypes and allele frequencies were analyzed by the chi-square test. Logistic regression analysis identified hypertension as a factor that increased IA risk (P = 1.0 x 10(-4); OR, 2.500; 95%CI, 1.573-3.972); IA was associated with two SNPs in the TSLC2A9 gene: rs7660895 (P = 0.007; OR, 1.541; 95%CI, 1.126-2.110); and in the TOX gene: rs11777927 (P = 0.013; OR, 1.511; 95%CI, 1.088-2.098). Subsequent removal of the influence of family relationship identified between 12 of 119 patients enhanced the significant association of these SNPs with IA (P = 0.001; OR, 1.691; 95%CI, 1.226-2.332; and P = 0.006; OR, 1.587; 95%CI, 1.137-2.213 for rs7660895 and rs11777927, respectively). Fur-thermore, the minor allele of rs7660895 (A) was also associated with IA rupture (P = 0.007; OR, 2.196; 95%CI, 1.230-3.921). Therefore, hypertension is an independent risk factor for IA. Importantly, the TSL-C2A9 (rs7660895) and TOX (rs11777927) gene polymorphisms may be associated with formation of IAs, and rs7660895 may be associated with IA rupture.

[Metrology analysis and thoughts of literatures on tinnitus associated with sudden deafness based on CiteSpace].

Objective: To explore the incidence of sudden deafness accompanied with tinnitus, the selection of examination protocols and treatment, and to provide reference for the establishment of new guidelines for sudden deafness. Methods: CiteSpace software was used for analysis and data mining to analyze and summarize the computer-retrieved articles on diagnostic examination and treatment of sudden deafness accompanied with tinnitus collected from CNIC, Wanfang and Web of Science databases from 2011 to 2021. Results: A total of 207 randomized controlled studies were retrieved in this study, including 121 in Chinese and 86 in English. Finally, 74 Chinese literatures and 16 English literatures were included. Among the 74 valid Chinese literatures, 64 (86.5%) were accompanied with tinnitus, 58 (78.4%) with dizziness/vertigo, 25 (33.8%) with aural fullness, 10 (13.5%) with headache, 4 (5.4%) with insomnia, 4 (5.4%) with a mixture of dizziness and tinnitus, and 2 (2.7%) with vomiting. Among the 16 English literatures, 15 (93.8%) were accompanied with tinnitus, 12 (75.0%) with vertigo, 1 (6.3%) with aural fullness, and 1 (6.3%) with a mixture of various symptoms. Among the 64 Chinese articles mentioning tinnitus, only 9 mentioned tinnitus matching tests, and 1 mentioned that the treatment for tinnitus accompanying symptoms was sound therapy and psychological counseling. The incidence rates of tinnitus accompanying four different types of sudden deafness, from low to high, are as follows: low-to-mid frequency, 82.4%; mid-to-high frequency, 90.7%; complete deafness, 92.4%; and flat type, 92.8%. Conclusion: Tinnitus is the most common accompanying symptom of sudden deafness, and tinnitus matching test is an effective evaluation method. When establishing a scientific, comprehensive, and systematic diagnosis and treatment system or guidelines for sudden deafness, attention should be paid to the diagnosis and treatment of tinnitus symptoms and their adverse psychological reactions, in order to reduce the incidence of tinnitus patients in the later stage of recovery from sudden deafness.

[A multicenter study on the effects of congenital cytomegalovirus infection on hearing loss].

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement (RR=4.58,95%CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group (RR=0.90, 95%CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL (OR=11.58, 95%CI 2.10-63.93, P=0.005) and preterm birth (OR=4.98, 95%CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.