The mechanism of Danzikang Knee Granule in regulating the chondrogenic differentiation of mesenchymal stem cells based on TGF-ß signaling pathway in cartilage repair in knee osteoarthritis.

This study aimed to explore the mechanism of Danzikang Knee Joint Granules in regulating the differentiation of mesenchymal stem cells into cartilage to cartilage repair of knee osteoarthritis based on the TGF-ß signaling pathway. For this purpose, 60 SD rats were divided into four groups; the control group and treated groups with low, medium, and high concentrations of Danzikang. The histopathology of rats was analyzed and TGF-ß signaling pathway-related proteins were determined. Results showed that the average optical density in serum of the Danzikang Granule intervention group was significantly higher than the control group (P<0.05), and the average optical density increased with drug concentration increasing (P<0.05). Compared with the control group, Danzikang knee granule cell survival in the intervention group was elevated the serum and reduced cell apoptosis rate (P < 0.05). Danzikang knee infusion concentrations were positively correlated with bone marrow mesenchymal stem cell survival rates (P < 0.05), and negatively correlated with apoptosis rate (P < 0.05). TGF-ß1, BMP2, and BMP4 were significantly increased in the three concentrations of the Danzikang Granule serum intervention group (P<0.05). TGF-ß1, BMP2 and BMP4 were significantly increased in the high concentration group, while TGF-ß1, BMP2 and BMP4 were significantly decreased in the low concentration group (P<0.05). The Wakitani histological score of the control group was significantly lower than the other three groups (P<0.05). In general, Danzikang Knee Granule plays a role in cartilage repair in knee osteoarthritis by promoting mesenchymal stem cell proliferation and cartilage differentiation, and the specific mechanism may be related to TGF-ß1/BMPs signaling pathway.

Overexpression of constitutively active MAP3K7 in ameloblasts causes enamel defects of mouse teeth.

OBJECTIVE: Compelling evidence suggests that mitogen-activated protein kinases (Mapks) play an important role in amelogenesis. However, the role of transforming growth factor (TGF)-ß-activating kinase 1 (Tak1, Map3k7), which is a known upstream kinase of Mapks, during amelogenesis remains to be determined. The aim of this study was to investigate the possible involvement of Map3k7 in amelogenesis. DESIGN: We generated transgenic mice that produced constitutively active human MAP3K7 (caMAP3K7) under the control of amelogenin (Amelx) gene promoter. Radiography and micro-computed tomography (µCT) analysis was used to detect the radio-opacity and density of the teeth. The enamel microstructure was observed with a scanning electron microscope. Histological analysis was used to observe the adhesion between ameloblasts and residual organic matrix of the enamel. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of enamel matrix protein. RESULTS: The enamel of mandibular molars in caMAP3K7-overexpressing mice displayed pigmentation and a highly irregular structure compared with the wild type littermates. Teeth of transgenic animals underwent rapid attrition due to the brittleness of the enamel layer. The microstructure of enamel, normally a highly ordered arrangement of hydroxyapatite crystals, was completely disorganized. The gross histological appearances of ameloblasts and supporting cellular structures, as well as the expression of the enamel protein amelotin (Amtn) were altered by the overexpression of caMAP3K7. CONCLUSIONS: Our data demonstrated that protein expression, processing and secretion occurred abnormally in transgenic mice overexpressing caMAP3K7. The overexpression of caMAP3K7 had a profound effect on enamel structure by disrupting the orderly growth of enamel prisms.

Analysis on clinical efficacy and influencing factors of decitabine-based regimens in patients with myelodysplastic syndrome-refractory anemia with excess blasts / 中国医师杂志

Objective To analyze the clinical efficacy,safety and influencing factors of decitabine (DAC)-based regimens in patients with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB).Methods We performed a retrospective analysis of 63 patients with MDS-RAEB treated with DAC,evaluated the clinical efficacy and adverse reactions,and analyzed the influencing factors affecting survival.Results Among 63 patients,23 were RAEB-1 and 40 were RAEB-2.The median treatment was 4 (2-13) courses.The total effective rate of DAC for MDS-RAEB was 58.7％ (37/63),and the complete response rate was 20.6％ (13/63).Among 37 patients who were effective,20 (54.1％) patients performed efficacy after 2 courses.The median course of treatment to achieve the best effect was 3.5 (3-4) courses.With a median follow-up of 14 (2-68) months,63 patients had a overall survival rate (OS) of 84.2％ and a 1-year progression-free survival rate (PFS) of 73％.In univariate analysis,the factors that prolonged OS were that the best effect after medication was stable disease (SD) (to achieve complete remission,partial remission,complete bone marrow remission,hematological improvement) (P =0.009) and no thrombocytopenia at first diagnosis (P =0.019),the factor that prolongs PFS is the best effect above SD (P =0.003).Multivariate analysis suggested that the factors affecting OS and PFS were the best curative effects above SD (P =0.015 vs P =0.008).The adverse effects of decitabine in the treatment of MDSRAEB were mainly bone marrow suppression and pulmonary infection.Conclusions Decitabine is an effective and well-tolerated drug in the treatment of MDS-RAEB.Response to decitabine treatment is one of the independent factors affecting the prognosis.

Application of domestic porcine antihuman lymphocyte immunoglobulin in allogeneic hemopoietic stem cell transplantation for severe aplastic anemia / 中国医师进修杂志

Objective To investigate the efficacy of domestic porcine antihuman lymphocyte immunoglobulin (p-ALG) in the treatment of severe aplastic anemia (SAA) with allogeneic hemopoietic stem cell transplantation (HSCT). Methods The clinical data of 5 SAA patients who received allogeneic HSCT from January 2015 to May 2018 were retrospectively analyzed. The conditioning regimen included p-ALG + cyclophosphamide + fludarabine. The method of peripheral stem cell and bone marrow blood was used in allogeneic HSCT (the total amount of bone marrow blood was less than 400 ml and the puncture point was not replaced). The p-ALG related complications, post-transplantation hemopoietic stem cell reconstitution time and efficacy were recorded. Results Allergic reaction occurred in 1 patient when using p-ALG, and there was no serum reaction. Hemopoietic reconstitution was achieved in all the 5 patients. The time for neutrophilic granulocyte > 0.5 × 109/L was 11 to 17 d, and the time for platelet count > 20 × 109/L was 11 to 15 d after transplantation. The results of short-strand repeat polymerase chain reaction assays showed all complete donor chimera. Graft versus host disease occurred in 3 cases, and was successfully controlled by methylprednisolone and tacrolimus. The time for stopping red blood cell transfusion was 9 to 87 d. The patients were followed up for 1 to 37 months, and the patients all survived well. Conclusions The efficacy of p-ALG in SAA patients of allogeneic HSCT is affirmative, and the cost is obviously reduced. It is worthy of clinical use.

Prenatal echocardiographic diagnosis and differential diagnosis of fetal double outlet ventricle / 中华超声影像学杂志

Objective To investigate the clinical value of prenatal diagnosis of fetal double outlet ventricle . Methods T he data of double outlet ventricle from fetal echocardiography in Second Xiangya Hospital of Central South University and Changde Women and Children Health Hospital of Hunan Province from January 2000 to August 2018 were collected . T he statistical method was used to analyze characteristics of echocardiography ,related‐intracardiac and extracardiac abnormalities ,postnatal echocardiography ,surgery and autopsy findings . Results Ninety‐four fetuses were diagnosed with double outlet ventricle ,including 84 cases of double outlet right ventricle ( DORV ) and 10 cases of double outlet left ventricle ( DOLV ) . T he pregnancy was terminated in 45 cases . Autopsy was offered to all patients after termination of pregnancy ,42 cases were consistent with prenatal diagnosis ,1 case was tetralogy of fallot ,2 cases were transposition of great artery . Forty‐nine cases were decided to continue the pregnancy ,32 cases of them were confirmed by postpartum surgery ,17 cases were confirmed by postnatal echocardiography . Echocardiographic findings of fetal double outlet ventricle was characterized by the origin of the both great arteries arising predominantly or completely( ＞50% ) from the same ventricle . Conclusions Prenatal ultrasound diagnosis of double outlet ventricular has important clinical value ,facilitate appropriate prenatal counseling and postnatal management and it should be differentiated with transposition of the great arteries ,tetralogy of fallot and ventricular septal defect .

Prevalence of gastric cancer and its correlation with Helicobacter pylori infection in Enshi Tujia and Miao Autonomous Prefecture in 2011-2020 / 公共卫生与预防医学

Objective Based on the incidence and mortality of gastric cancer and the correlation with helicobacter pylori (Hp) infection in Enshi Tujia and Miao Autonomous Prefecture from 2011 to 2020, the prevalence trend of gastric cancer in this decade was analyzed, providing theoretical basis for the prevention and treatment of gastric cancer in Enshi Tujia and Miao Autonomous Prefecture. Methods According to the unified national examination and evaluation standards, 15 tumor registries meeting the requirements were selected in Enshi Tujia and Miao Autonomous Prefecture. The incidence and death data of gastric cancer were collected, and the incidence and death rates were analyzed by gender and age. The normalized incidence rate and Hp positive rate of enshi city, Lichuan city and six counties including Jianshi, Badong, Xuan 'en, Xianfeng, Laifeng and Hefeng were compared. Spearman correlation analysis was used to analyze the correlation between standard incidence rate and Hp positive rate of gastric cancer in each district of Tujia and Miao Autonomous Prefecture of Enshi Prefecture. Results Both male and female had an upward trend. The average rate of standard incidence of gastric cancer in male and female was 4.07% and 4.15%, respectively, and there was no significant difference in the trend of standard incidence rate in different genders (P>0.05). The gross death rates and standardized death were decreased in both male and female. The average decreasing rate of standardized death rate of gastric cancer in males and females was -3.91% and -4.12%, respectively, and there was no significant difference in the trend of standardized death rate in different genders (P>0.05). Overall, the incidence rate in age group 50-80 from 2016 to 2020 was significantly higher than that from 2011 to 2015 (P<0.05). The mortality rate in the 60-80 age group from 2016 to 2020 was significantly lower than that from 2011 to 2015 (P<0.05). The trend of morbidity and mortality in different age groups was consistent in the two periods. There was a positive correlation between the incidence standard rate of gastric cancer and Hp positive rate (r =0.473, P<0.05). Conclusion From 2011 to 2020, the incidence and mortality of gastric cancer in Enshi Tujia and Miao Autonomous Prefecture were both at a high level, with an upward trend and a downward trend. The positive rate of Hp and the new infection rate of Hp in the high incidence area of gastric cancer were higher than those in the low incidence area.

Bone morphogenetic protein receptor Ⅱ signaling pathway and pulmonary arterial hypertension:updates and expectations / 中国药理学与毒理学杂志

The identification of the relationships between mutations of the bone morphogenetic protein type Ⅱ receptor (BMPR2) and pulmonary arterial hypertension (PAH) has been considered to be one of the most significant discoveries in this area in the 21st century. And BMPR2 mutation is responsible for the majority of hereditary PAH as well as some of idiopathic PAH. Furthermore, clinical and animal expreimental research over the past few years has revealed that BMPR2 signaling pathway plays a critical role in the initiation and progress of PAH, by participateing in the pathogenesis of PAH. In addition, the potential that BMPR2 signaling pathway is used as a therapeutic target is being evaluated. This review summarizes our current understanding of the role of BMPR2 mutations in PAH from the perspectives of genetics, epigenetics, inflammation as well as interactions with other significant pathways.

Development of tone-pip auditory brainstem responses and auditory steady-state responses in infants aged 0-6 months.

CONCLUSIONS: The longitudinal findings presented in this study suggest that with the maturational development, the conduction time of the auditory nerve decreases while the thresholds had no physiological changes within 0-6 months after birth. Comparing the tone-pip auditory brainstem response (ABR) with the auditory steady-state response (ASSR), the former had lower thresholds than the latter at 500-8000 Hz, which indicates that the estimation of tone-pip ABR maybe nearer to the actual hearing level of infants. OBJECTIVE: To evaluate the feasibility of tone-pip ABR and ASSR for newborns and infants, and to follow the development of the threshold estimates from tone-pip ABR and ASSR in normal infants through the first 6 months of life. METHODS: The tone-pip ABR and ASSR thresholds were measured at octave frequencies from 250 to 8000 Hz bilaterally in 80 infants aged 0-6 months with normal hearing. RESULTS: For click ABR at 70 dB nHL, the absolute and inter-peak wave latencies decreased as the age increased. The tone-pip ABR had similar waveforms to the click ABR, its wave latencies decreased and the waveforms improved as the age and frequency increased. On average, the thresholds of tone-pip ABR and ASSR were observed at 1.2-41.2 dB nHL (SD = 2.6-8.0 dB) and 16.9-43.0 dB nHL (SD = 2.5-8.0 dB), respectively, at 250-8000 Hz in infants aged 0-6 months, but there were no physiological differences. Tone-pip ABR thresholds were significantly lower than those for ASSR except at 250 Hz (p < 0.05). Both ASSR and ABR had stable and similar audiograms in the different groups.

Study of newborn hearing and genetic screening in Jinan / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>In this study, we employed newborn hearing screening and gene screening concurrently to explore the hearing loss associated with mutations in the city of Jinan.</p><p><b>METHODS</b>A total of 3 288 newborns born between March 2013 and December 2013 in Jinan Maternity and Child Care Hospital received hearing concurrent genetic screening. Transiently evoked otoacoustic emissions (TEOAE) was used in rooming-in newborns, while TEOAE and auto auditory brainstem response (AABR) was used in infants in neonatal intensive care unit (NICU). Two drops of heel blood were harvested with filter paper. Nine mutations [GJB2 (235delC, 35delG, 299delAT, 176del16), SLC26A4 (IVS7-2A>G,2168 A>G), GJB3 (538 C>T), 12SrRNA (1555 A>G, 1494C>T)] of 4 frequent genes associated with Chinese hearing loss were determined by gene chip in these dried blood samples.</p><p><b>RESULTS</b>Among 3 288 newborns, 363 cases failed to pass the hearing screening, and 36 cases of these 363 newborns carried mutations, with a carrier rate of 9.91%. 2 925 cases passed the hearing screening, of which 113 carried mutations, with a carrier rate of 3.86%. There was a significantly statistic difference (χ2=8.67, P=0.000) in carrier rate between two groups. 149 (4.53%) infants were detected to carry at least one mutation allele,among which 113 cases passed the hearing screening and 36 cases failed. Seven cases were diagnosed to have hearing loss. Homozygous GJB2 mutation was detected in 2 cases, compound heterozygous GJB2 mutation was detected in 1 case, and heterozygous GJB2 mutation in 88 cases. There were 91 cases carried GJB2 mutations totally, with a total rate of 2.76%. There were 40 cases were detected to carry heterozygous SLC26A4 mutation, with a carrier rate of 1.22%. Nine cases had heterozygous GJB3 mutation, with a carrier rate of 0.27%. Six cases had homogeneous mitochondria 12SrRNA mutation, and 1 had heterogeneous mutations. There were 7 cases totally, with a total rate of 0.21%. 142 infants with gene mutation should be follow-up.</p><p><b>CONCLUSION</b>A follow-up system in infants, passed hearing screening,with single heterozygous mutation and mutations associated with drug-induced hearing loss, can help to detect infants with hearing defects early and effectively prevent late-onset hearing impairment.</p>

Antimicrobial resistance rate of Pseudomonas aeruginosa and it’s correla-tion with antimicrobial use density / 中国感染控制杂志

Objective To realize antimicrobial resistance rate of Pseudomonas aeruginosa (P. aeruginosa)and it’s correlation with antimicrobial use density(AUD),and to provide reference for control of healthcare-associated infec-tion.Methods From July 2011 to December 2013,antimicrobial resistance rate of P. aeruginosa isolated from hospi-talized patients and AUD of patients were monitored,and the correlation between them was analyzed.Results AUD of patients decreased from 73.61 in the third and fourth quarters of 2011 to 41.33 in the same quarters of 2013. Corre-lation coefficient of AUD and antimicrobial resistance rate of P. aeruginosa was -0.32~0.88,correlation coeffi-cient of resistance rate of P. aeruginosa to aztreonam and aztreonam use density was 0.88,there was statistical sig-nificance. Conclusion AUD of hospitalized patients revealed a decreasing tendency,suggesting antimicrobial selec-tive resistance should be considered in clinic.

Study on Hydrolysis Reaction of Novel Camptothecin Derivative(L-P) Using Capillary Zone Electrophoresis / 分析化学

Capillary zone electrophoresis (CZE) was developed to investigate the structure stability of novel camptothecin derivative (L-P) at different pH,the kinetics and thermodynamics of hydrolysis reaction from lactone form to carboxylate form direction at near physiological conditions (pH 7.4,310 K). Uncoated fused-silica capillaries(35 cm×50 μm i. d,with effective length of 26.5 cm) were used. The background electro-lyte( BGE) was 0.025 mol/L sodium phosphate buffer with pH varied at 2.5,4.0,5.0,6.0,7.0,7.4 and 9. 0. The electrophoresis voltage was maintained at 14 kV when the pH of BGE ranged between 2.5 and 5.0,otherwise,the voltage was maintained at 10 kV. The UV detector was set at 260 nm. All samples were introduced using hydrodynamic injection at 5 kPa for 4 s. L-P was found to be lactone form as the solution pH was below 4. 0. As pH increased,the lactone form of L-P would undergo hydrolysis reaction to be carboxylate form. As pH was 9.0,L-P existed almost completely as carboxylate form. The rate constant of the hydrolysis increased as temperature raise. The energy of activation ( Ea) ,the enthalpy ( ΔH) and entropy (ΔS) of the hydrolysis reaction were determined as 72. 6 kJ/mol,10. 5 kJ/mol and 50. 9 J/( mol K) ,respectively. The proposed capillary zone electrophoresis could efficiently separate two pH-dependent structural forms of the novel camptothecin derivative( L-P). The positive enthalpy and entropy values of the L-P hydrolysis indicated that the reaction was endothermic and entropically driven and higher temperature favored.

A case-control study on high-risk factors for newborn hearing loss in seven cities of Shandong province / 华中科技大学学报（医学）（英德文版）

To investigate the high-risk factors for newborn hearing loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn hearing screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn't pass the hearing screening received audiological and medical evaluation and 367 were confirmed to have hearing loss. Of them, 177 neonates with hearing loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity, history of receiving treatment in neonatal intensive care unit (NICU), neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity (OR=16.285, 95% CI 3.379-78.481), neonatal disease (OR=34.968, 95% CI 2.720-449.534), family history of congenital hearing loss (OR=69.488, 95% CI 4.417-1093.300) and birth weight (OR=0.241, 95% CI 0.090-0.648). It is concluded that parity, neonatal disease and family history of hearing loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.

A Case-control Study on High-risk Factors for Newborn Hearing Loss in Seven Cities of Shandong Province / 华中科技大学学报（医学）（英德文版）

To investigate the high-risk factors for newborn heating loss and to provide information for preventing the development of hearing loss and delaying its progression, from May 2003 to June 2006, neonates who failed to pass the universal newborn hearing screening (UNHS) were referred to Jinan Newborn Hearing Screening and Rehabilitation Center from 7 newborn heating screening centers in seven cities of Shandong province. One-to-one pair-matched case-control method was employed for statistical analysis of the basic features of definitely identified cases. High-risk factors relating to the bilateral hearing loss were evaluated by univariate and multivariate Logistic regression analysis. Our results revealed that 721 transferred newborns who didn't pass the heating screening received audiological and medical evaluation and 367 were confirmed to have heating loss. Of them,177 neonates with heating loss who met the matching requirements were included in the study as subjects. Univariate analysis showed that high-risk factors related to hearing loss incuded age of father, education backgrounds of parents, parity, birth weight, gestational weeks, craniofacial deformity,history of receiving treatment in neonatal intensive care unit (NICU), neonatal disease, family history of otopathy and family history of congenital hearing loss. Multivariate Logistic regression analysis revealed that 4 independent risk factors were related to bilateral hearing loss, including parity (OR=16.285, 95% CI 3.379-78.481), neonatal disease (OR=34.968, 95% CI 2.720-449.534),family history of congenital hearing loss (OR=69.488, 95% CI 4.417-1093.300) and birth weight (OR=0.241, 95% CI 0.090-0.648). It is concluded that parity, neonatal disease and family history of hearing loss are the promoting factors of bilateral hearing loss in neonates and appropriate intervention measures should be taken to deal with the risk factors.