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.

Background and Aims:In recent years,function-preserving proximal gastrectomy with reconstruction has become an important approach for the treatment of early gastric cancer.However,there is no standardized surgical technique,and the short-and long-term outcomes of various new procedures remain unclear.This study was performed to evaluate the safety and short-term efficacy of laparoscopic proximal gastrectomy plus esophagogastrostomy with single-flap technique for early gastric cancer. Methods:The clinical data and follow-up records of 7 patients who underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy in the First Affiliated Hospital of Soochow University between December 2021 and December 2022 were retrospectively analyzed.Perioperative safety,postoperative reflux,anastomotic stricture at 6 months,and related nutritional parameters were assessed.The nutrition-related indicators of this group of patients were compared with those of 11 patients who underwent total gastrectomy with Roux-en-Y anastomosis for early gastric cancer during the same period. Results:All 7 patients successfully underwent laparoscopic proximal gastrectomy with single-flap esophagogastrostomy.The average operative time was(212.9±20.6)min,with anastomosis taking(54.7±10.5)min;the mean intraoperative blood loss was(28.6±9.0)mL.No Clavien-Dindo grade Ⅲ or higher complications were observed during hospitalization.None of the patients experienced significant reflux symptoms,although 1 patient developed anastomotic stricture 3 months after operation.There were no statistically significant differences in hemoglobin concentration,albumin level,prealbumin level,total protein concentration,and lymphocyte count between preoperative and 6-month postoperative measurements(all P＞0.05).Compared to patients who underwent total gastrectomy with Roux-en-Y anastomosis,those who had the proximal gastrectomy with single-flap esophagogastrostomy showed a lower percentage decrease in body weight,skeletal muscle area at the third lumbar vertebra(L3),visceral fat area at L3,and hemoglobin concentration at 1 year after operation(all P＜0.05). Conclusion:Laparoscopic proximal gastrectomy with single-flap esophagogastrostomy is a safe and feasible surgical option for early gastric cancer,offering effective anti-reflux outcomes while minimizing the risk of anastomotic stricture.This procedure has a lower impact on postoperative nutritional status compared to total gastrectomy.

Objective To explore the impact of the sialic acid binding lectin-E(Siglec-E)on the inhibitory properties of parthenolide(PTL)against lipopolysaccharide(LPS)-induced M1 polarization of microglia(BV2).Methods ①Single cell sequencing data of Siglece related mouse brain tissue was obtained from Gene Expression Omnibus(GEO)database and divided into the WT group(n=3)and the Siglece-/-group(n=4).The microglia cells were screened,and the enrichment analysis was performed to analyze related differential genes and pathways.BV2 cells were constructed by the shRNA interference technique and were divided into NC-shRNA and Siglece-shRNA to detect the expression level of Siglec-E(Siglece).② NC-shRNA and Siglece-shRNA cells were respectively divided into the Control group,LPS group,PTL group and PTL+LPS group(n=3).The mRNA levels of markers of M1 polarization in microglia,iNOS,IL-1 β and IL-6,were detected by RT-qPCR.Siglecefl/fl and Cx3cr1cre mice were mated to obtain microglia-specific Siglece deletion(Siglecefl/fl×Cx3cr1cre)mice,and LPS-induced neuroinflammation model was established.③ Nine WT and Siglecefl/fl×Cx3cr1cre male mice were assigned to the Control group,LPS group and PTL+LPS group(n=3).RT-qPCR,immunofluorescence assay and Western blotting were used to verify the knock-out effect and polarization-related pathways,and to investigate the mechanism of Siglec-E affecting PTL inhibition of M1 polarization of microglia.Results Compared with the NC-shRNA group,the expression of Siglec-E in the Siglece-shRNA group was significantly decreased(P<0.01),indicating that the Siglec-E knock-down cell model was successfully established.With the stimulation of LPS,mRNA levels ofiNOS,IL-1 β and IL-6 were significantly up-regulated compared with the Control group both in shRNA cells and Siglece-shRNA cells(P<0.01).With the influence of PTL and LPS,the markers of M1 polarization in NC-shRNA cells mentioned before were significantly decreased(P<0.05),while for Siglice-shRNA cells,there were no significant changes in the markers of M1 polarization.PTL inhibited the phosphorylation of JNK and IκB protein(P<0.01)and the nuclear translocation of NF-κB in BV2 cells,down-regulated Siglec-E,and weakened the inhibitory effect.Compared with mice in the WT group,the expression of Siglec-E in microglia of Siglecefl/fl×Cx3cr1cre mice was decreased significantly(P<0.01),and the inhibitory effect of PTL on the phosphorylation of NF-κB in microglia of Siglecefl/fl×Cx3cr1cre mice was also decreased.Conclusion The absence of Siglec-E in microglia attenuates the inhibition of M1 polarization by the MAPK/NF-κB pathway targeted by PTL.

Objective:To establish an environmental management strategy for the prevention of ventilator-associated pneumonia from the perspective of etiological characteristics and to verify its application effect.Methods:Based on a sampling survey, this study constructed preventive management strategies for ventilator-associated pneumonia by blocking pathogen characteristics from the perspective of both colonization and infection management in patients. From July 2021 to June 2023, a non-synchronous randomized controlled study was conducted, including a control group of 59 cases and an experimental group of 57 cases from ICU of Tianjin Teda Hospital, all of them were mechanically ventilated patients. The effectiveness of the strategy was confirmed.Results:In the control group, there were 35 males and 24 females, with an average age of (46.97 ± 18.84) years. In the experimental group, there were 39 males and 18 females, with an average age of (47.49 ± 13.85) years. During the study period, there were 9 cases of ventilator-associated pneumonia (VAP) in the control group and 2 cases in the experimental group, the difference between the two groups was statistically significant (exact odds ratio=0.031). The duration of mechanical ventilation in the experimental group (122.41 ± 18.36) h, which was shorter than that in the control group (187.62 ± 18.05) h, and the difference was statistically significant ( t=19.28, P<0.05). The length of ICU stay in the experimental group was (8.38 ± 0.79) d, in the control group was (10.99 ± 1.10) d, the difference between them was statistically significant ( t=14.66, P<0.05). On the 7th day, there were 7 cases of positive pathogenic bacteria in sputum culture in the experimental group, which was significantly different from the 29 cases in the control group ( χ2=16.73, P<0.05). Conclusions:The vector management strategy for preventing ventilator-associated pneumonia by blocking etiological characteristics can reduce the incidence of VAP, shorten the duration of mechanical ventilation and ICU stay, and reduce the pathogen load in the sputum of mechanically ventilated patients on the 7th day.

OBJECTIVE To study the protective effect and possible mechanism of soybean isoflavones against threatened miscarriage rats. METHODS Female mice were selected to promote estrus and mate with male mice. After pregnancy， they were randomly divided into normal group （purified water， i.g.， n＝10）， model group （purified water， i.g.， n＝9）， positive control drug group （progesterone 4 mg/kg， i.m.， n＝9）， low-， medium- and high-dose soybean isoflavone groups （25， 50 and 100 mg/kg， i.g.， n＝10）. Except for the normal group， the rest were given mifepristone+misoprostol on the 8th day of pregnancy to establish threatened miscarriage model， and then given purified water or drugs， once a day， on days 1-7 and 9-12 of pregnancy， respectively. At 14 days of pregnancy， the rates of fetal protection were counted. Serum levels of β-human chorionic gonadotrophin （β-HCG） and progesterone （P） in rats were detected. Pathological and morphological changes in rat placenta and decidua tissues were observed， and the apoptosis indexes of cells were detected； mRNA and protein expressions of factor of apoptosis related （Fas）， factor of apoptosis related ligand （FasL）， proliferating cell nuclear antigen （PCNA） and heparin binding epidermal growth factor （HB-EGF） were determined in placenta tissues， and mRNA and protein expressions of Fas， PCNA and HB-EGF in decidua tissues were detected. RESULTS In the model group， the placental tissues of rats were hyperemia and dilatation， with fewer and irregular blood vessels； severe stromal edema，inflammatory cell infiltration and iron-choledrin depositionwere observed. Compared with model group， the fetal survival rates， serum levels of β-HCG and P， the expressions of PCNA and HB-EGF mRNA and proteins in the placenta and decidua tissue of soybean isoflavone groups increased significantly （P＜ 0.05）， while pathological changes were improved significantly； cell apoptosis index in the placenta and decidua tissue， the expressions of Fas， FasL mRNA and proteins in the placenta and Fas mRNA and protein in the decidua tissue decreased significantly （P＜0.05）. The effect of soybean isoflavones was dose-dependent （P＜0.05）. CONCLUSIONS Soybean isoflavone has protective effect on threatened miscarriage， the mechanism of which is related to down-regulating the expressions of Fas and FasL mRNA and protein at the maternal-fetal interface， and up-regulating the expressions of mRNA and protein of PCNA and HB- EGF.

Objective: To investigate the function and potential mechanism of hepatocellular carcinoma(HCC) cells-derived extracellular nicotinamide phosphoribosyl transferase(eNAMPT) in the angiogenesis of human umbilical vein endothelial cells(HUVEC). Methods: The eNAMPT secretion of HCC cells were stimulated by hypoxia treatment and investigated the angiogenesis of HUVEC was investigated by tube formation assays. Transcriptomic RNA sequencing(RNA-seq) analyses of HUVEC under eNAMPT treatment were used to explore the mechanism of the effect of eNAMPT-insulin receptor(INSR) axis on angiogenesis. Western blot was used to detect the effects of eNAMPT-INSR axis on protein expression of HUVEC cells. qRT-PCR was used to detect the influence of eNAMPT-INSR axis on the expression of HUVEC intracellular related target genes. Results: ELISA and Western blot results showed that the protein level of eNAMPT in the culture supernatant of HCC cells increased significantly after hypoxia stimulation.In vitroangiogenesis assay results showed that eNAMPT significantly increased the nodules number and total length of tubes in HUVEC. The transcriptome sequencing results of HUVEC showed that eNAMPT, as an insulin analogue, participated in the regulation of biological processes such as cell migration and angiogenesis in HUVEC, and might promote angiogenesis by activating insulin-like signaling pathways. Western blot results showed that the eNAMPT-INSR axis affected p-AKT and p-ERK1/2 protein levels in PI3K-AKT and MAPK-ERK1/2 signaling pathways in HUVEC. qRT-PCR results showed that the eNAMPT-INSR axis affected the expression of angiogenesis related target genes MMP2, MMP9 and VEGF in HUVEC. Conclusion eNAMPT secreted by HCC cells promotes angiogenesis by binding INSR to activate the PI3K-AKT and MAPK-ERK1/2 signaling pathways.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.

Objective:To validate the feasibility of the gamma analysis method in the study of prescription dose conversion between logistic nanodosimetry model (LNDM) and microdosimetric kinetic model (MKM) basing on the Chinese self-developed model LNDM by applying clinical experiences of National Institute of Radiological Science (NIRS).Methods:Physical dose distributions derived from the MKM- and LNDM-based carbon ion treatment plans were compared via the method of gamma analysis under the open-source treatment planning platform matRad. In this way, the prescribed dose conversion factor between the MKM- and LNDM-based treatment plans was obtained. Using water phantoms, the influence of geometric shape, size, depth of target volume (TV), prescribed dose and field setting on the conversion factor was investigated comprehensively. Moreover, preliminary verification of the acquired conversion factor was conducted on the C-shape model and a case of liver cancer patient.Results:The conversion factor depended on the field setting rather than the TV shape. Under the condition of single field, the conversion factor was positively correlated with the size and depth of TV, and the prescribed dose. Moreover, the conversion factor was successfully verified using the C-shape model and the patient with liver cancer, where the gamma passing rates (2%/2 mm) of the physical dose distribution generated by the MKM and LNDM treatment plans were 92.79% and 91.19%, respectively.Conclusions:The conversion factors (f=D LNDM/D MKM) obtained in this study might provide guidance for the prescribed dose setting during the carbon ion treatment planning based on the LNDM. Besides, the gamma analysis method could be used for the study of the prescribed dose conversion between different models.

Background The contradiction between science and operability has always existed in the model of classified occupational health supervision and management. Comprehensive risk assessment method for occupational disease hazards of employers provides risk grading and classification for occupational health management, and it's a new attempt to explore classification supervision and law enforcement. Objective To apply a comprehensive risk assessment method for occupational disease hazards of employers to estimate health risk level of wood furniture enterprises, discuss its advantages and disadvantages, and provide a basis for improving the classified management of occupational health. Methods Seven typical factories were selected in counties with highly concentrated wooden furniture manufacturing. Occupational health field investigation and testing were carried out to estimate occupational disease hazard risk level (Ⅰ, Ⅱ, and Ⅲ). A self-rated checklist was applied to score occupational health management status by interviewing employers, one by one, and to determine occupational health management status grade (A, B, and C) by the score. Thus, a comprehensive risk level (Class A, Class B, and Class C) of a specific factory was obtained from a matrix of occupational disease hazard risk level and management status grade. Risk verification was carried out based on any abnormality reported by regular occupational physical examination in past 3 years. Results Defects in occupational health management were identified in all 7 factories, among which 6 were grade C with key nonconformities (poor), and 1 was grade B (medium). Disqualified occupational disease hazards were found in 6 of 7 factories, and the workstation-specific disqualified rates were 26.09% (12/46) for noise, 14.71% (5/34) for wood dust (hard), and 12.50% (1/8) for xylene. Level Ⅱ (medium) of occupational disease hazard risk was estimated in 5 of 7 factories, while level Ⅲ (high) in 2 factories. All 7 factories were class C (high risk) accessed by the comprehensive risk assessment method for occupational disease hazards. The occupational health surveillance documents showed 636 batches of regular occupational physical examination were ordered by the 7 employers, and a total of 37 workers from 5 factories reported abnormalities in physical examination, among which 3 workers reported dust exposure and 34 workers reported noise exposure. Conclusion The comprehensive risk assessment method for occupational disease hazards of employers is not able to perform with satisfaction in occupational health classification of wooden furniture manufacturing factories yet. It is necessary to expand the pilot to improve this assessment method and develop an efficient supervision mechanism to ensure the authenticity of the data before it is popularized and applied in classified occupational health management.

Renal hematuria is caused by glomerular damage and basement membrane rupture due to coagulation dysfunction， ischemia and hypoxia， and immune function damage， resulting in red blood cells exuding through glomerular filtration membrane and excreting with urine. It is mainly manifested as microscopic and macroscopic hematuria. Among them， microscopic hematuria is characterized by microscopic urine sediment examination， there are three or more red blood cells per high-power microscopic field. Traditional Chinese medicine （TCM） believes that the pathogenesis of renal hematuria always belongs to ''asthenia in origin and sthenia in superficiality''， and ''asthenia in origin'' is caused by the deficiency of the three viscera of the lung， spleen， and kidney， while ''sthenia in superficiality'' is caused by the combination of dampness and blood stasis and the external disturbance of wind pathogens. The key pathogenesis features are ''deficiency， dampness， heat， blood stasis， and wind''. After consulting the TCM literature related to renal hematuria， the author found that the common syndrome types of renal hematuria in clinical practice were the deficiency of both Qi and Yin， the deficiency of both Yin and fire， the unsteadiness of kidney Qi， the deficiency of spleen and kidney Yang， the wind heat hurting the collateral， the dampness-heat blocking， and the blood stasis and internal resistance. The commonly used classical or temporal prescriptions included Shenqi Dihuangtang（参芪地黄汤）， Zhibai Dihuangtang（知柏地黄汤）， Wubi Shanyaowan（无比山药丸）， Jisheng Shenqiwan（济生肾气丸）， Sishenwan（四神丸）， Yinqiaosan（银翘散）， Bazhengsan（八正散）， Sanrentang（三仁汤）， Xuefu Zhuyutang（血府逐瘀汤）， Danggui Shaoyaosan（当归芍药散）， Xiaoji Yinzi（小蓟饮子）， Buzhong Yiqitang（补中益气汤）， et al. Self prepared prescriptions mainly include Tongluo Ningxue prescription （通络宁血方）， Qingre Zhixue prescription（ 清热止血方） and Wuteng Tongluo drink （五藤通络饮）. The traditional Chinese medicine is commonly used for the treatment of Xueniaoling granules（血尿灵冲剂）， Xueniaoan capsules（血尿安胶囊）， Ningmitai capsules（宁泌泰胶囊）， Huangkui capsules（黄葵胶囊） and Yishen nixuexiao granules（益肾溺血消颗粒）， which constantly enriched the treatment of renal hematuria. The combination of TCM and western medicine has obvious advantages. The treatment of renal hematuria in clinical practice often combines with modern medical methods， which has a good therapeutic effect on the improvement of symptoms and indicators of renal hematuria. At present， many doctors have made in-depth exploration on the etiology， pathogenesis， and clinical treatment of renal hematuria， but few scholars have made detailed induction and collation in recent years. Therefore， the author has collated the clinical data on the treatment of renal hematuria with TCM in the past ten years， and reviewed it from the aspects of etiology， pathogenesis， and clinical research， to provide useful references for clinical intervention and delay the progress of renal disease.