BACKGROUND:Osteoblasts are the main cell types responsible for bone formation and remodeling,and the normal performance of their function is precisely regulated by various signaling pathways.Among them,the bone morphogenetic protein and Wnt signaling pathways play a key role in osteogenesis. OBJECTIVE:To review the role of bone morphogenetic protein/Wnt signaling pathway in the regulation of osteoblast function and analyze its changes in different physiological and pathological conditions in order to further reveal the molecular mechanism of bone formation and remodeling. METHODS:The Chinese and English search terms"BMP signaling pathway,Wnt signaling pathway,and osteogenesis"were searched in CNKI,Wanfang,and PubMed databases for original researches published from the inception to June 2023.Totally 61 articles were finally selected for analysis and summary.Using the method of the literature review,the studies of the bone morphogenetic protein/Wnt signaling pathway in regulating osteogenesis were sorted out and analyzed. RESULTS AND CONCLUSION:(1)Bone morphogenetic protein and Wnt signaling pathways play important roles in the differentiation,proliferation,and maturation of osteoblasts.Bone morphogenetic protein signaling pathway mainly regulates the expression of osteogenesis-related genes through the activation of Smad protein.Smad protein enters the nucleus and regulates the expression of genes related to osteogenesis.Different Wnt signaling pathway from bone morphogenetic protein mainly depends on the activation of β-catenin to exert its biological effects.(2)The regulatory effect of bone morphogenetic protein/Wnt signaling pathway will be affected by many factors in different physiological and pathological states.Growth factors,hormones,and mechanical stress can affect the activity of bone morphogenetic protein/Wnt signaling pathway to some extent.(3)Bone morphogenetic protein/Wnt signaling pathway interacts with other signaling pathways in the regulation of osteogenesis,and they together constitute a complex regulatory network.(4)Chinese medicine and natural compounds can promote bone health by regulating signaling pathways,providing new possibilities for treating bone diseases.(5)Future studies can further explore the interaction of bone morphogenetic protein/Wnt signaling pathway and other signaling pathways and its changes in different physiological and pathological conditions,resolve the key nodes and regulation mechanism in the complex network,to provide more precise targets for the treatment of bone-related diseases,and also provide new ideas to reveal the molecular mechanism of bone formation and remodeling.

Objective To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis. Methods The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model. Results A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ² = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ² = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period (t = −0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant (b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models (t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05). Conclusions The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT3R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+ and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT3R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT3Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT3Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and the γ-aminobutyric acid(GABA)"disinhibition"mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT3R-induced GABA"disinhibition"mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT2R-mediated regulation of anxiety reactions are also activated by 5-HT3R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT3Rs.However,given the circuit specific modulation of 5-HT3Rs on emotion,systemic use of 5-HT3R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT3R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

Traumatic cerebrospinal fluid leakage commonly presents in traumatic brain injury patients, and it may lead to complications such as meningitis, ventriculitis, brain abscess, subdural hematoma or tension pneumocephalus. When misdiagnosed or inappropriately treated, traumatic cerebrospinal fluid leakage may result in severe complications and may be life-threatening. Some traumatic cerebrospinal fluid leakage has concealed manifestations and is prone to misdiagnosis. Due to different sites and mechanisms of trauma and degree of cerebrospinal fluid leak, treatments for traumatic cerebrospinal fluid leakage varies greatly. Hence, the Craniocerebral Trauma Professional Group of Neurosurgery Branch of Chinese Medical Association and the Neurological Injury Professional Group of Trauma Branch of Chinese Medical Association organized relevant experts to formulate the " Chinese expert consensus on the diagnosis and treatment of traumatic cerebrospinal fluid leakage in adults ( version 2023)" based on existing clinical evidence and experience. The consensus consisted of 16 recommendations, covering the leakage diagnosis, localization, treatments, and intracranial infection prevention, so as to standardize the diagnosis and treatment of traumatic cerebrospinal fluid leakage and improve the overall prognosis of the patients.

【Objective】 To investigate the resource allocation status of blood testing laboratories in 14 blood stations in Gansu Province, explore the impact of differences in basic conditions on the comprehensive testing ability of laboratories, so as to promote the homogenization and standardization of blood screening capacity in blood stations in Gansu and improve blood safety and effectivenes. 【Methods】 An evaluation index system of laboratory resource allocation was constructed and a question-naire was designed. The data of human resources, infrastructure and key equipment of 14 blood stations were collected. The entropy weight -TOPSIS method was used to evaluate and rank the resource allocation of 14 blood stations. 【Results】 In the comprehensive evaluation of blood testing laboratory resource allocation in 14 blood stations in Gansu, the top three were laboratories A, B and I, and the last three were laboratories G, M and J. On the whole, the main issue was unreasonable structure of human resources: most laboratories had unreasonable age structure; except for Laboratory A, there was no personnel with bachelor's degree or above in laboratories; most laboratories had not established a team with intermediate professional titles. In terms of infrastructure, the size of seven laboratories could not meet the needs of modern laboratory testing, and all eight blood stations had no spare nucleic acid laboratories nor a mutual spare laboratory with other blood stations As for the key equipment, 5 laboratories had no automatic blood grouping diagnostic instrument, 5 laboratories only had one set of enzyme immunoassay detection system, 3 laboratories had no spare equipment for the key equipment, which means if the equipment failure could not be repaired in time, the release of results would be affected. 【Conclusion】 There were significant differences in human resources, infrastructure and key equipment of blood testing laboratories in 14 blood stations in Gansu, which had a great impact on laboratory testing capacity and subsequent development. It is suggested that governments at all levels and health administrative departments optimize the input of laboratory resource allocation according to the blood collection volume of blood stations to gradually narrow the differences in resource distribution between different regions, improve the degree of laboratory automation and optimize the personnel structure, so as to build high-quality and efficient blood testing laboratories and ensure the safety of clinical blood use.

Objective:To study the impact of donor left hepatic vein classification and the reconstruction methods on hepatic venous outflow obstruction (HVOO) after pediatric living-donor liver transplantation using left lateral liver segments.Methods:A retrospective study was performed on the clinical data of 653 children recipients who underwent living-donor liver transplantation with left lateral liver segments from January 2014 to December 2020 at Tianjin First Central Hospital. There were 309 males and 344 females, aged 7.0 (6.0, 10.0) months, with an age range of 3-121 months. Based on the left hepatic vein on preoperative donor enhancement CT as well as the intraoperative reconstruction methods, the recipients were divided into 3 groups: type Ⅰ group ( n=514), anastomosis using a single opening was performed directly between the donor and the recipient; type Ⅱ group ( n=118), angioplasty was performed on two adjacent recipient venous orifices before anastomosis, and type Ⅲ group ( n=21), an interposition vessel was anastomosed to two widely spaced openings or the two veins were anastomosed separately. The preoperative general status of the patient, postoperative HVOO incidences, and graft and recipient survival rates were compared among the three groups. The patients were followed up by outpatient reexamination or telephone. Results:Graft to recipient weight ratio in the type Ⅲ group was smaller than that in the type Ⅰ group and the type Ⅱ group ( P<0.05). For all the 653 patients, the incidence of postoperative HVOO was 4.59% (30/653), with the incidences of HVOO in the 3 groups of patients were 4.1% for the type Ⅰ group (21/514), 5.1% for the type Ⅱ group (6/118), and 14.3% for the type Ⅲ group (3/21), respectively. There was no significant difference among the groups ( P>0.05). The recipient cumulative survival rates at 1 and 3 years after surgery in the type I group were 97.8% and 97.0%, and the corresponding rates in the type Ⅱ group were 96.5% and 94.2%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. There was a significant difference between the type Ⅰ and type Ⅲ groups ( P=0.048). The graft cumulative survival rates at 1 and 3 years in the type Ⅰ group were 97.4% and 96.9%, and the corresponding rates in the type Ⅱ group were 94.9% and 92.5%, and in the type Ⅲ group were 94.1% and 86.9%, respectively. The difference in the postoperative graft cumulative survival rates between the type Ⅰ group and type Ⅱ group was significant ( P=0.044). Conclusions:The anatomy of the left hepatic vein supplying the left lateral liver segment was highly variable, and the majority of the variations could be reconstructed. A reasonable reconstructive method could reduce the incidence of postoperative HVOO and improved the outcomes of the graft.

Objective:To explore the impact of graft recipient weight ratio(GRWR)on pediatric whole liver transplantation in infants aged under 1 year.Methods:From January 2014 to December 2019, clinical data were retrospectively reviewed for 140 children aged under 1 year with whole liver transplantation.They were divided into 3 groups of low GRWR(GRWR<2.5%, 48 cases), middle GRWR(2.5%≤GRWR<5%, 73 cases)and high GRWR(GRWR≥5%, 19 cases). Basic profiles, major postoperative complications and survival rate of graft/recipient were compared.Results:There were 62 males and 78 females with an average age of (7.34±1.81)months and an average weight of(6.81±1.09)kg.The median GRWR was 3.27%(1.33%~8.12%). The higher level of GRWR, the greater age, weight and graft weight of donor in three groups and there was statistical difference ( P<0.05); operative duration, postoperative ICU stay and hospital stay were longer in low GRWR group than those in middle GRWR group and there was statistical difference( P<0.05); The incidence of postoperative hepatic artery thrombosis was higher in low GRWR group than that in middle GRWR group(31.3%vs 8.2%)and there was statistical difference( P<0.05); 4 cases of small-for-size syndrome occurred in low GRWR group, it was significantly different from the other two groups and there was statistical difference( P<0.05); the median follow-up period was(50.7±23.4)months.The survival rates of grafts at 3-month and 1/5-year were 89.6%, 91.8%, 100%; 87.5%, 87.7%, 100%; 87.5%, 87.7%, 100%and there was no inter-group difference( P>0.05). The survival rates of recipients at 3 months, 1 year and 5 years post-operation were 93.8%, 91.8%, 100%; 91.7%, 87.7%, 100%; 91.7%, 87.7%, 100%and there was no inter-group difference( P>0.05). Conclusions:Different from pediatric living donor transplantation, GRWR≥5%does not affect the survival rate of recipient/graft during whole liver transplantation.And GRWR<2.5%may boost the postoperative incidence of hepatic artery thrombosis and small liver syndrome.

Objective:To investigate the associations between small diffusion-weighted imaging (DWI) hyperintensities lesions and total cerebral small vessel disease (cSVD) burden and the influence on prognosis in patients with acute intracerebral hemorrhage (ICH).Methods:Consecutive patients with acute spontaneous ICH from January 2018 to June 2021 were recruited in the Stroke Center of Zhengzhou People′s Hospital. Magnetic resonance imaging was performed to quantify DWI hyperintensities lesions and cSVD imaging markers, including white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds, which were calculated for the total cSVD burden (0-4 points). The prognosis was assessed with the modified Rankin Scale (mRS) at discharge and 90-day. Multivariable Logistic regression models were adopted to explore the associations between DWI lesions and total cSVD burden and clinical outcome.Results:Of 283 included patients, 59 (20.8%) had small DWI lesions, 32 (11.3%) had multiple lesions. They were mostly punctate, mainly located in the cortical and subcortical regions, and scattered in multiple vascular territories. With the increase of cSVD burden, the number of DWI lesions gradually increased. Spearman correlation analysis showed that the total cSVD burden was positively correlated with the number of DWI lesions ( r=0.21, P<0.001). In multivariable regression analyses, the total cSVD burden was independently associated with DWI lesions ( OR=1.63, 95% CI 1.23-2.15, P=0.001). The 90-day poor outcome (mRS scores≥4) in patients with DWI lesions was significantly higher than those without DWI lesions (39.3% vs 16.3%, χ 2=14.38, P<0.001), while there was no statistically significant difference in the poor outcome of discharge between the two groups (26.5% vs 17.7%, χ 2=3.06, P=0.080). With the increase in the number of DWI lesions, the 90-day poor outcome increased significantly (trend chi-squared test χ 2=11.50, P=0.001). Multivariable analyses showed that DWI lesions ( OR=4.39, 95% CI 1.92-10.03, P<0.001) and their number ( OR=1.42, 95% CI 1.06-1.90, P=0.018) were independently associated with the 90-day poor outcome. Conclusions:Higher total cSVD burden is an independent risk factor for small DWI lesions in patients with ICH. Small DWI lesions were independently associated with the 90-day poor outcome, but not with the discharge outcome.

Objective:To investigate the effect of continuous intracranial pressure (ICP) and brain oxygen partial pressure (PbtO 2) monitoring and guiding treatment after the application of standard large bone flap decompression and microhematoma removal in patients with severe traumatic brain injury (TBI). Methods:A retrospective analysis was done of 41 patients with TBI in Department of Neurosurgery in the Inner Mongolia People's Hospital from January 2018 to May 2020. Patients with Glasgow coma scale (GCS)<8 points were treatesd with microscopical removal of hematoma and contusion brain tissue and standard large bone flap decompression. Intraoperative intracranial pressure and brain tissue oxygen partial pressure monitoring probes were placed. Postoperatively, continuous intracranial pressure monitoring and partial oxygen pressure monitoring of brain tissue were performed, and target-based treatment under ICP and PbtO 2 monitoring was performed. According to the Glasgow Outcome (GOS) score after six months, patients were divided into a good outcome group (4-5 scores) and a poor outcome group (1-3 scores). There were 26 cases in good prognosis group and 15 cases in poor prognosis group. Linear regression analysis was used to further evaluate the relationship between PbtO 2, ICP and GOS score. The measurement data of normal distribution were compared by independent sample t-test. The counting data were expressed in cases (%), and the comparison between groups was adopted χ 2 inspection. The general linear bivariate Pearson correlation test was used. Results:The mean value of PbtO 2 (17.42±5.34) mmHg in the poor prognosis group was lower than that in the good prognosis group (24.65±5.61) mmHg, with statistical significance ( t=4.04, P<0.001). The mean value of ICP (22.32±3.45) mmHg in the poor prognosis group was higher than that (17.32±3.23) mmHg in the good prognosis group, with statistical significance ( t=4.15, P<0.001). Using PbtO 2 and ICP as independent variables and GOS score after 6 months as dependent variable, a regression equation was established ( Y=4.040 X+7.497; Y=-2.549 X+28.63). The mean value of PbtO 2 was positively correlated with GOS scores after 6 months in patients with severe head injury ( r=0.75, P<0.001). The mean value of ICP was negatively correlated with the prognosis of patients with severe head injury ( r=-0.87, P<0.001). Conclusion:The treatment guided by ICP combined with PbtO 2 monitoring is valuable in improving the prognosis of patients with severe traumatic brain injury after standard decompressive craniectomy, and may improve the prognosis 6 months after the injury.