Objective To detect the osteopontin (OPN) autocrine function of the osteoclasts in neurofibromatosis type 1 heterozygote (Nfl+/-) and wild type (Nfl+/+) mice.Test the osteoclasts function of neurofibromatosis type 1 heterozygote (Nfl+/-) and wild type (Nil+/+) mice with exogenous neutralizing OPN antibody,analysis the role of autocrine OPN in the hyperfunction of osteoclast in neurofibromatosis type 1.Methods Culture the low density bone marrow cells from Nfl heterozygote (Nfl+/-) and wild type (Nfl+/+) mice (4-6 weeks old) with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand(RANKL),Measure.the OPN concentration in osteoclast culture superenant with ELISA.Culture the low density bone marrow cells from Nf1+/-and Nf1+/+ mice with or without exogenous neutralizing antibody for OPN.The function of osteoclasts and osteoclast progenitors in formation,migration,adhesion,and bone absorption were tested.Results A significantly higher concentration of OPN was detected in the Nf1+/-osteoclast culture media as compared to that of wild type.In control,Osteoclast functions,including migration,adhesion,and bone resorption of Nf1 +/-were higher than that of wild type.Addition OPN neutralizing antibody to the Nf1+/-OCL significantly reduced OCL formation.Neutralizing OPN antibody diminished both wild type and Nf1+/-OCL adhensiontion,Anti-OPN minimized OCL migration in both wild type and Nf1 +/-OCL cultures as measured by the transwell assays.Neutralizing OPN antibody diminished both wild type and Nf1+/-OCL pit formation,P＞0.05 for comparing Nfl+/-vs.wild type OCLs with anti-OPN antibody.Conclusion The hyperfunction of osteoclast in Nf1 heterozygote is related with autocrine osteopontin,inhibition of OPN may be an effective treatment for bone destruction of neurofibromatosis type 1.

The objective of the present study was to establish a method based on principal component analysis (PCA) for the study of transdermal delivery of multiple components in Chinese medicine, and to choose the best penetration enhancers for the active fraction of Xiangfusiwu decoction (BW) with this method. Improved Franz diffusion cells with isolated rat abdomen skins were carried out to experiment on the transdermal delivery of six active components, including ferulic acid, paeoniflorin, albiflorin, protopine, tetrahydropalmatine and tetrahydrocolumbamine. The concentrations of these components were determined by LC-MS/MS, then the total factor scores of the concentrations at different times were calculated using PCA and were employed instead of the concentrations to compute the cumulative amounts and steady fluxes, the latter of which were considered as the indexes for optimizing penetration enhancers. The results showed that compared to the control group, the steady fluxes of the other groups increased significantly and furthermore, 4% azone with 1% propylene glycol manifested the best effect. The six components could penetrate through skin well under the action of penetration enhancers. The method established in this study has been proved to be suitable for the study of transdermal delivery of multiple components, and it provided a scientific basis for preparation research of Xiangfusiwu decoction and moreover, it could be a reference for Chinese medicine research.

Objective To analyze the types and epidemiological characteristics of influenza virus in Xi'an during 2009 to 2017.Methods A total of 21 856 samples of throat swabs from patients with influenza like illness ( ILI) were collected from 5 national influenza sentinel surveillance hospitals from August 2009 to December 2017.Influenza virus nucleic acid was detected by real-time fluorescence quantitative PCR and virus types were confirmed , chick-embryo cells or Madin-Darby canine kidney (MDCK) cells were used to isolate influenza virus.SPSS 18.0 software was used for data analysis.Results The positive detection rate of influenza virus was 16.19%(3 539/21 856), the seasonal influenza A virus subtypes including H1, H3, the new type H1and H7 accounted for 62.39%(2 208/3 539), influenza B virus subtypes including Victoria , Yamagata and unclassified type B accounted for 37.50%( 1 327/3 539), and the mixed influenza virus infection accounted for 0.11%(4/3 539).The positive rate of influenza virus detected in different years was significantly different ( χ2＝357.651, P ＜0.01).During January to March the major influenza A viruses accounted for 49.07%(947/1 930), influenza B viruses accounted for 50.93%(983/1 930); during October to December , the influenza A viruses accounted for 78.07%( 1 061/1 359 ), and influenza B viruses accounted for 21.93%( 298/1 359 ); there was significant difference in composition of type A virus and type B virus between different seasons ( χ2＝ 550.06, P＜0.05).The positive detection rate of influenza virus in patients with ILI of age groups 0-3 years,＞3-7 years,＞7-13 years,＞13-18 years,＞18-24 years,＞24-60 years and ＞60 years were 12.61%, 19.41%, 19.66%, 22.98%, 14.91%, 13.50% and 12.84%, respectively ( χ2＝202.52, P＜0.05).Conclusion Influenza A virus is common in Xi'an,winter and spring are the peak seasons for influenza epidemics.It is recommended for susceptible people to take influenza vaccination .

Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis.

BACKGROUND:Scaffold materials serve as platforms that provide space and structure,playing a crucial role in the regeneration of cartilage tissue.Scholars from around the world are exploring different approaches to fabricate more ideal scaffold materials. OBJECTIVE:To review the design principles and preparation methods of cartilage scaffolds,and to further explore the advantages and limitations of various preparation methods. METHODS:Literature searches were conducted on the databases of CNKI,WanFang Data,PubMed,and FMRS from 1998 to 2023.The search terms were"cartilage repair,cartilage tissue engineering,cartilage scaffold materials,preparation"in Chinese and English.A total of 57 articles were ultimately reviewed. RESULTS AND CONCLUSION:(1)The articular cartilage has a unique structure and limited self-repair capacity after injury.Even if self-repair occurs,the newly formed cartilage is typically fibrocartilage,which is far inferior to normal articular cartilage in terms of structure and mechanical properties.It is difficult to maintain normal function and often leads to degenerative changes.Currently,the design and fabrication of scaffold materials for cartilage repair need to consider the following aspects:biocompatibility and biodegradability,suitable pore structure and porosity,appropriate mechanical properties,and bioactivity.(2)Research on the preparation of cartilage scaffolds has made significant progress,continuously introducing new preparation methods and optimization strategies.These methods have their advantages and disadvantages,providing more possibilities for customized preparation and functional design of cartilage scaffolds according to specific requirements.

BACKGROUND:Bone formation is the process by which osteoblasts synthesize and secrete osteoid and promote its mineralization,which generally involves mechanical signal transduction.Osteoblasts are primarily regulated by mechanical factors such as gravity,compressive stress,tensile stress,fluid shear stress,and hydrostatic pressure in vivo,and different mechanical stimuli modulate the proliferation,differentiation,and apoptosis of osteoblasts through various mechanisms,including hormones,cytoskeletal proteins,and microRNAs.By clarifying the effects of biomechanical forces on osteoblasts,it provides ideas and a reference basis for the treatment of osteometabolic diseases involving osteoblasts. OBJECTIVE:To review the effects of different biomechanical forces on the biological characteristics of osteoblasts. METHODS:We conducted a literature search using PubMed,Web of Science,FMRS,CNKI,and WanFang databases for relevant publications published from 2000 to 2023,covering basic research and tissue engineering studies related to the effects of biomechanical forces on osteoblasts.Ultimately,a total of 70 articles were reviewed. RESULTS AND CONCLUSION:Different biomechanical forces have an impact on the biological characteristics of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are dependent on the intensity and duration of the applied force.Specifically,the effects are as follows:(1)Under microgravity conditions,osteoblast proliferation and differentiation are inhibited,resulting in a decrease in bone density and the development of osteoporosis.(2)Compared to microgravity,hypergravity has a promoting effect on osteoblast proliferation.(3)The effects of compressive stress on osteoblasts are dependent on the loading intensity and time.Appropriate compressive stress can promote osteoblast proliferation and differentiation,which is beneficial for bone tissue formation and repair,while excessive compressive stress can cause osteoblast apoptosis and bone tissue destruction.(4)The biological effects of different types of tensile stress on osteoblasts differ.Studies have shown that a strain rate within the range of 0-12%has a promoting effect on osteoblast proliferation.(5)Fluid shear stress can promote osteoblast proliferation and differentiation and enhance the bone-inducing effect of biomaterials.(6)Static hydrostatic pressure can affect the biological behavior of osteoblasts,including proliferation,differentiation,and apoptosis,and these effects are closely related to the time and intensity of the pressure.Understanding the effects of different biomechanical forces on osteoblasts is of great significance for a deeper understanding of bone growth and maintenance mechanisms.

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Objective:To investigate the factors affecting the effect of periprostatic nerve block (PNB), establish a prediction model of pain degree, and verify the prediction efficiency.Methods:The clinical data of 314 patients who underwent transperineal prostate biopsy in our hospital from June 2022 to January 2023 were retrospectively analyzed. The median age was 71 (65, 76) years, the median prostate-specific antigen (PSA) was 14.6 (10.70, 24.65) ng/ml, and the median puncture needle number was 21 (19, 23) needles, median prostate volume 45.86 (31.52, 67.96) ml, median body mass index (BMI)24.02(22.97, 25.33)kg/m 2, including 109 patients with a history of diabetes, 90 patients with a history of surgery, and 57 patients with a history of severe trauma. The patients were divided into mild pain group (1-3 points), moderate pain group (4-6 points) and severe pain group (7-10 points) according to the intraoperative visual analogue scale (VAS). According to the clinical characteristics, the factors affecting the effect of PNB were analyzed by univariate analysis and multiple ordered logistic regression method. R language was used to construct a nomogram model for predicting PNB effect, receiver operating characteristic (ROC) curve and calibration curve were drawn, and Hosmer-Lemeshow test was carried out to verify the prediction efficiency of the model. Results:The results of univariate analysis showed that 171 patients in the mild pain group had a median age of 71 (65, 75) years, a median PSA14.5 (9.6, 24.6) ng/ml, a median number of puncture needles of 20 (18, 22), and a median prostate volume of 34.94 (26.36, 45.12) ml, median BMI24.17(23.14, 25.79)kg/m 2, including 74 patients with a history of diabetes, 51 patients with a history of surgery, and 40 patients with a history of severe trauma; There were 110 patients in the moderate pain group, the median age was 71 (65, 76) years, the median PSA14.8 (11.03, 24.27) ng/ml, the median number of puncture needles was 23 (20, 24) needles, median prostatic volume 63.24 (49.14, 78.72) ml, median BMI23.91(22.58, 24.88)kg/m 2, including 26 patients with a history of diabetes, 29 patients with a history of surgery, and 10 patients with a history of severe trauma; In the severe pain group, 33 patients had a median age of 73 (67, 78) years, a median PSA14.6 (10.85, 34.80) ng/ml, and a median puncture needle number of 23 (22.5, 24) needles, median prostate volume 70.64 (61.50, 104.51) ml, median BMI24.32(23.00, 26.06)kg/m 2, including 9 patients with a history of diabetes, 10 patients with a history of surgery, and 7 patients with a history of severe trauma. The results of univariate analysis showed that the number of puncture needles ( P<0.01), prostate volume ( P<0.01), history of diabetes ( P=0.002) and history of major trauma ( P= 0.009) were the factors affecting the effect of PNB. Multiple logistic regression analysis showed that puncture needle number ( P=0.009), prostate volume ( P<0.01) and diabetes history ( P=0.041) were independent risk factors for PNB effect. The area under ROC curve (AUC) of the moderate and above pain prediction model was 0.872, P<0.01; the area under ROC curve of the severe pain prediction model was 0.817, P<0.01; the result of Hosmer-Lemeshow test of the moderate and above pain prediction model was χ2=5.001, P=0.757. The results of the severe pain prediction model were χ2=4.452 and P=0.814. The calibration curve was established, which showed that the prediction probability of pain degree was in good agreement with the actual risk. Conclusions:The number of puncture needles, prostate volume and history of diabetes are the risk factors affecting the effect of PNB. The prediction model of PNB effect based on this model can be used to predict the pain degree of patients undergoing prostate biopsy after PNB.

L-Homoserine is a non-essential amino acid that is often used as an important platform compound and additive in industrial production. To improve the production efficiency, a previously constructed L-homoserine producing strain E. coli H0-0 was used as a chassis for further metabolic modification. Firstly, the ppc and pyccgP458S genes were overexpressed to optimize the Kreb's cycle. Subsequently, thrAC1034T and lysCcgC932T were overexpressed to improve the product synthesis, followed by inactivation of iclR gene to reduce the accumulation of by-products. The introduction of three sucrose metabolism genes, scrA, scrB and scrK, enabled E. coli to ferment sucrose. The titer of L-homoserine increased from 3.2 g/L to 11.1 g/L.
Escherichia coli/genetics* ; Homoserine ; Metabolic Engineering ; Serine

Objective·To explore the immune-related characteristics of non-small cell lung cancer(NSCLC),discover potential tumor markers in V-J genes,and lay the foundation for establishing a TCR-antigen recognition prediction model.Methods·A total of 704 NSCLC samples were collected to establish a comprehensive T-cell receptor(TCR)repertoire analysis workflow.The upstream analysis included steps such as raw data processing,quality control,filtering,TCR sequence identification,and extraction.The downstream analysis included repertoire clone distribution,clone typing,V-J gene sharing,CDR3 distribution characteristics,and clone tracking.The sample clone distribution was analyzed by using indices such as Shannon-Weiner index and Chaol index.Clone typing was performed based on the number of clone amplifications to explore differences among different types.The degree of V-J gene segment sharing was analyzed,and the sharing of low-frequency clone types was determined through clone amplification weight analysis of V-J genes by using two samples of papillary thyroid carcinoma.Finally,analysis of the distribution characteristics of V genes and high-frequency clone type CDR3,and clone tracking analysis were conducted to monitor changes in tumor immune clone frequencies before and after analysis,aiming to identify potential tumor markers.Results·① Significant differences were observed in clone distribution and clone typing among different NSCLC tissues,as well as among different ages and genders.② Specific highly-shared V-J genes were identified in the analysis of V-J gene sharing,and non-normal distribution of high-clone V genes and amino acid high-frequency clone types were found in the CDR3 distribution analysis.③ In the analysis of high-frequency clone type clone tracking,highly expressed or newly expressed high-frequency clone types were observed in NSCLC,suggesting that these clone types could serve as potential tumor-associated antigens or bind with CDR3 reference sequences of new antigens.④ It was found that the expression frequency of TRBJ2-5 gene,originally low-expressed,significantly increased,indicating its potential role as a key low-frequency gene in tumor immune response.Conclusion·The TRAV21 and TRBV6.5 genes show high clone amplification in NSCLC and could serve as potential tumor biomarkers.