OBJECTIVES: To analyze bone mass distribution and the factors affecting bone mass in a general Chinese Han cohort undergoing physical examinations at our center. METHODS: We retrospectively collected the data of bone mineral density (BMD) measurements from 30 599 healthy Han Chinese adults (age≥20 years) who underwent dual-energy X-ray absorptiometry scans at our hospital from July, 2013 to July, 2023. Basic parameters including height, body weight, and gender were recorded, and descriptive statistics and correlation analyses were performed using R software. RESULTS: In this cohort, the male individuals had a mean peak BMD of 1.00±0.12 g/cm² in the lumbar vertebrae, 0.94±0.14 g/cm² in the femoral neck, and 0.99±0.13 g/cm² in the total hip, significantly higher than the values in the female individuals [0.99±0.12 g/cm² in the lumbar vertebrae (P=0.022), 0.79±0.11 g/cm² in the femoral neck (P<0.001), and 0.88±0.11 g/cm² in the total hip (P<0.001)]. In the overall cohort, the BMD values of the lumbar spine and femur decreased with age after reaching their peak levels. There was a positive correlation between BMD value and body mass index (BMI) in both male and female individuals. The 2013-2014 period recorded the lowest BMD values in the lumbar, hip, and femoral neck, which tended to increase steadily in the following years (2015-2023). CONCLUSIONS Our data suggest that the BMD values vary among different populations, and future multi-center studies using more accurate BMD detection technology are warranted to capture the variation patterns of BMD with demographic characteristics of specific populations.
Humans ; Bone Density ; Absorptiometry, Photon ; Male ; Female ; Retrospective Studies ; Osteoporosis/diagnostic imaging* ; Adult ; Middle Aged ; Lumbar Vertebrae/diagnostic imaging* ; China/epidemiology* ; Femur Neck/diagnostic imaging* ; Aged ; Beijing/epidemiology* ; Young Adult

OBJECTIVE To screen the primary processing methods of Ligusticum sinense slice based on differential metabolites， and provide theoretical basis for the scientific processing of L. sinense. METHODS Using 13 groups of L. sinense slice processed by fresh-cutting or traditional methods as samples， UHPLC-QE-MS was employed for metabolite identification. Multivariate statistical analysis was applied to screen differential metabolites among the 13 sample groups， analyzing the effects of washing， soaking， drying methods， and drying cycles on both the relative expressions of differential metabolites and the contents of carboxylic acids and their derivatives in the samples （to reflect the total amino acid content）. RESULTS Principal component analysis and partial least squares-discriminant analysis both showed significant intergroup differences among the 13 sample groups. A total of 688 differential metabolites were screened from the 13 sample groups， with carboxylic acids and their derivatives showing the highest proportion. The relative expression levels of phosphatidylcholine significantly increased after washing treatment， while tryptophan expression significantly decreased after soaking treatment. Samples dried at 50-60 ℃ showed significantly increased expression of psoralen， whereas those dried at 40 ℃ showed significantly decreased expression of methyl -p- methoxycinnamate. Both washing and soaking treatments significantly reduced the total amino acid content in samples， while secondary drying significantly increased it. The three controlled-temperature drying methods maintained relatively stable total content of amino acids in samples. CONCLUSIONS The optimal processing protocol for L. sinense slice is as follows: fresh L. sinense slice should be freshly cut at the production site， undergo quick washing after soil removal， and be dried twice at 40 ℃ （before and after slicing）.

OBJECTIVE To establish a quantitative analysis of multi-components by single-marker （QAMS） method for simultaneous determination of six flavonoids and two phenolic acids in Perilla frutescens leaves using scutellarin and rosmarinic acid as internal reference substances， and apply this method to determine the contents of eight components in 20 batches of P. frutescens leaves samples from different regions. METHODS Scutellarin served as the internal reference to calculate relative correction factors （RCFs） for scutellarin-7-O-diglucuronide， luteolin-7-O-diglucuronide， apigenin-7-O-diglucuronide， luteolin-7-O- β-D-glucuronide and apigenin-7-O-glucuronide. Rosmarinic acid was employed as the internal reference to determine the RCF for caffeic acid. The contents of the above flavonoids and phenolic acids were calculated with QAMS， and compared with the results of external standard method. RESULTS The eight analytes demonstrated excellent linearity within their respective concentration ranges （r≥0.999 0）. The mean recovery rates for spiked samples ranged from 95.60% to 102.15%， with relative standard deviations （RSDs） of 0.72% to 2.70% （n＝6）. The method exhibited good precision， repeatability， and stability （RSD＜2.50%， n＝6）. Variations in instruments， columns， column temperature， flow rate， and formic acid volume fraction had minimal impact on the RCFs （RSD＜3%， n＝3）. Comparison with the external standard method showed no significant differences in the content of each component across batches， except for caffeic acid in the ZS12 batch （absolute value of RE＜5%， n＝2）. The contents of six CARS-21） flavonoid components in P. frutescens leaves samples varied significantly across different geographic origins， while the content of total flavonoids showed no significant difference. In contrast， the contents of two phenolic acid components and total phenolic acid exhibited significant variation among samples from different regions. CONCLUSIONS The developed QAMS method can simultaneously determine the contents of six flavonoids and two phenolic acids in P. frutescens leaves. It is convenient for detection， highly accurate， and cost-effective. This method is suitable for the quality control of P. frutescens leaves， and the variation of flavonoid and phenolic acid content in samples from different regions provides a reference for the selection of optimal cultivation areas.

OBJECTIVE: To propose a semi-supervised material quantitative intelligent imaging algorithm based on prior information perception learning (SLMD-Net) to improve the quality and precision of spectral CT imaging. METHODS: The algorithm includes a supervised and a self- supervised submodule. In the supervised submodule, the mapping relationship between low and high signal-to-noise ratio (SNR) data was constructed through mean square error loss function learning based on a small labeled dataset. In the self- supervised sub-module, an image recovery model was utilized to construct the loss function incorporating the prior information from a large unlabeled low SNR basic material image dataset, and the total variation (TV) model was used to to characterize the prior information of the images. The two submodules were combined to form the SLMD-Net method, and pre-clinical simulation data were used to validate the feasibility and effectiveness of the algorithm. RESULTS: Compared with the traditional model-driven quantitative imaging methods (FBP-DI, PWLS-PCG, and E3DTV), data-driven supervised-learning-based quantitative imaging methods (SUMD-Net and BFCNN), a material quantitative imaging method based on unsupervised learning (UNTV-Net) and semi-supervised learning-based cycle consistent generative adversarial network (Semi-CycleGAN), the proposed SLMD-Net method had better performance in both visual and quantitative assessments. For quantitative imaging of water and bone materials, the SLMD-Net method had the highest PSNR index (31.82 and 29.06), the highest FSIM index (0.95 and 0.90), and the lowest RMSE index (0.03 and 0.02), respectively) and achieved significantly higher image quality scores than the other 7 material decomposition methods (P < 0.05). The material quantitative imaging performance of SLMD-Net was close to that of the supervised network SUMD-Net trained with labeled data with a doubled size. CONCLUSIONS A small labeled dataset and a large unlabeled low SNR material image dataset can be fully used to suppress noise amplification and artifacts in basic material decomposition in spectral CT and reduce the dependence on labeled data-driven network, which considers more realistic scenario in clinics.
Tomography, X-Ray Computed/methods* ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Signal-To-Noise Ratio ; Perception

As human microbiome research advances, a large body of evidence shows that microorganisms are closely related to human health. Probiotics were discovered and used as foods or dietary supplements with health benefits in the last century. Microorganisms have shown broader application prospects in human health since the turn of the century, owing to the rapid development of technologies such as microbiome analysis, DNA synthesis and sequencing, and gene editing. In recent years, the concept of "next-generation probiotics" has been proposed as new drugs, and microorganisms are considered as "live biotherapeutic products (LBP)". In a nutshell, LBP is a living bacterial drug that can be used to prevent or treat certain human diseases and indications. Because of its distinct advantages, LBP has risen to the forefront of drug development research and has very broad development prospects. This review introduces the varieties and research advances on LBP from a biotechnology standpoint, followed by summarizing the challenges and opportunities for LBP clinical implementations, with the aim to facilitate LBP development.
Humans ; Probiotics ; Dietary Supplements ; Bacteria ; Drug Development ; Biotechnology

Objective:To observe the effect of early elevation of luteinizing hormone (LH) with flexible gonadotropin-releasing hormone antagonist (GnRH-A) protocol on pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer. Methods:A retrospective cohort study was conducted to analyze patients with normal ovarian reserve function who underwent IVF/ICSI with flexible GnRH-A protocol at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2021. According to the level of LH before antagonist addition, the patients were divided into two groups, group A: early elevation of LH (LH >10 U/L before the addition of antagonist, n=65), group B: the patients whose LH≤10 U/L before the addition of antagonist ( n=193), which was matched with group A using the 1∶3 propensity score matching by age, duration of infertility, anti-Müllerian hormone, body mass index and antral follicle count. The general conditions, clinical data, embryonic laboratory indicators and clinical outcomes were compared between the two groups. Results:There were no significant differences in the baseline characteristics between the two groups (all P>0.05). There were no significant differences in basic LH levels, gonadotropin (Gn) initiation dosage, total dosage and duration of Gn used, duration of Gn used when adding antagonists and estradiol (E 2) level on the trigger day between group A and group B (all P>0.05). The LH level [12.2 (11.1, 17.5) U/L], E 2 level [3 301.0 (2 708.0, 4 275.0) pmol/L] and follicle diameter [14.0 (12.6, 15.5) mm] were significantly higher in group A than in group B [3.5 (2.2, 5.2) U/L, 2 178.5 (1 208.0, 3 218.0) pmol/L, 13.0 (12.0, 14.0) mm] when adding antagonist (all P<0.001). The level of LH in group A decreased rapidly after adding antagonist, LH level in group A after antagonist application [3.4 (2.0, 5.2) U/L] and the LH level on the trigger day [3.0 (1.7, 4.7) U/L] were still higher than those in group B [2.1 (1.5, 3.3) U/L, P<0.001; 2.1 (1.4, 3.3) U /L, P=0.004], the level of progesterone on the trigger day was not significantly higher than that in group B ( P>0.05). There were no statistically significant differences in the number of oocytes retrieved, two pronuclei fertilization rate, the rate of high-quality embryo, the rate of blastocyst formation, endometrial thickness on the day of transplantation, the number of transferred embryos, the proportion of transferred blastocysts and the implantation rate between the two groups (all P>0.05). The clinical pregnancy rate, the early abortion rate, and the live birth rate were not statistically different between the two groups (all P>0.05). Conclusion:In patients with normal ovarian reserve, LH level was elevated early with antagonist flexible protocol, and decreased rapidly after the timely addition of antagonist, which did not lead to an increase of progesterone on the trigger day, and ultimately did not affect the clinical outcomes of IVF/ICSI fresh embryo transfer.

Objective:To observe the effect of early elevation of luteinizing hormone (LH) with flexible gonadotropin-releasing hormone antagonist (GnRH-A) protocol on pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) fresh embryo transfer. Methods:A retrospective cohort study was conducted to analyze patients with normal ovarian reserve function who underwent IVF/ICSI with flexible GnRH-A protocol at the Reproductive Medicine Center of the Third Affiliated Hospital of Zhengzhou University from January 2016 to September 2021. According to the level of LH before antagonist addition, the patients were divided into two groups, group A: early elevation of LH (LH >10 U/L before the addition of antagonist, n=65), group B: the patients whose LH≤10 U/L before the addition of antagonist ( n=193), which was matched with group A using the 1∶3 propensity score matching by age, duration of infertility, anti-Müllerian hormone, body mass index and antral follicle count. The general conditions, clinical data, embryonic laboratory indicators and clinical outcomes were compared between the two groups. Results:There were no significant differences in the baseline characteristics between the two groups (all P>0.05). There were no significant differences in basic LH levels, gonadotropin (Gn) initiation dosage, total dosage and duration of Gn used, duration of Gn used when adding antagonists and estradiol (E 2) level on the trigger day between group A and group B (all P>0.05). The LH level [12.2 (11.1, 17.5) U/L], E 2 level [3 301.0 (2 708.0, 4 275.0) pmol/L] and follicle diameter [14.0 (12.6, 15.5) mm] were significantly higher in group A than in group B [3.5 (2.2, 5.2) U/L, 2 178.5 (1 208.0, 3 218.0) pmol/L, 13.0 (12.0, 14.0) mm] when adding antagonist (all P<0.001). The level of LH in group A decreased rapidly after adding antagonist, LH level in group A after antagonist application [3.4 (2.0, 5.2) U/L] and the LH level on the trigger day [3.0 (1.7, 4.7) U/L] were still higher than those in group B [2.1 (1.5, 3.3) U/L, P<0.001; 2.1 (1.4, 3.3) U /L, P=0.004], the level of progesterone on the trigger day was not significantly higher than that in group B ( P>0.05). There were no statistically significant differences in the number of oocytes retrieved, two pronuclei fertilization rate, the rate of high-quality embryo, the rate of blastocyst formation, endometrial thickness on the day of transplantation, the number of transferred embryos, the proportion of transferred blastocysts and the implantation rate between the two groups (all P>0.05). The clinical pregnancy rate, the early abortion rate, and the live birth rate were not statistically different between the two groups (all P>0.05). Conclusion:In patients with normal ovarian reserve, LH level was elevated early with antagonist flexible protocol, and decreased rapidly after the timely addition of antagonist, which did not lead to an increase of progesterone on the trigger day, and ultimately did not affect the clinical outcomes of IVF/ICSI fresh embryo transfer.

Objective:To explore the effect of health education based on theory of planned behavior combined with stepped care model on negative emotion, psychological flexibility and quality of life in patients with lung cancer undergoing chemotherapy.Methods:From October 2020 to December 2021, 108 chemotherapy patients who underwent lung cancer surgery in Affiliated Hospital of Weifang Medical College and had anxiety or depression that scores was greater than 7 in any dimension of the Hospital Anxiety and Depression Scale (HADS) were selected as the study subjects. The study subjects were divided into observation group ( n=46) and control group ( n=48) by random digits table method. Routine care was implemented in the control group. The observation group implemented health education based on the theory of planned behavior combined with stepped care model intervention. The HADS scale was used every 4 weeks to assess negative emotion in both groups. In observation, patients with negative emotion relief stop the next stage of nursing intervention, and patients without relief continue the next stage of higher intensity nursing intervention. Results:Before the intervention, there were no significant difference in the scores of negative emotion, psychological flexibility and quality of life between the two groups ( P>0.05). After intervention, the scores of all dimensions of negative emotion and the total score in the observation group were significantly lower than those in the control group, and the differences had statistical significance ( t=4.86, 3.19 and 4.53, all P<0.05). After the intervention the scores of psychological flexibility and quality of life dimensions and the total score in the observation group were higher than those in the control group, the differences had statistical significance (t values were -6.01--2.89, all P<0.05). After the intervention, there was no significant difference in the remission rate of negative emotions between the clinical observation stage of the observation group and the concurrent control group ( P>0.05). The remission rates of guided self-help, problem-solving therapy, psychological or drug therapy and total negative emotions in the observation group were 38.46%(15/39), 33.33%(8/24), 6/16 and 78.26%(36/46), respectively, which were higher than those in the control group, and the differences had statistical significance ( χ2 values were 7.04 - 13.80, all P<0.05). Conclusions:Health education based on the theory of planned behavior combined with stepped care model can effectively alleviate the negative emotions of lung cancer patients undergoing chemotherapy and improve psychological flexibility and quality of life.

Objective:To establish osimertinib-resistant non-small cell lung cancer (NSCLC) cell line and explore its drug resistance mechanism.Methods:The human NSCLC cell line H1975 was used as the research object, and low-concentration osimertinib was used to continuously select secondary drug-resistant cell lines. Osimertinib drug sensitivity of cells was detected by MTS method. Cell proliferation was detected by live cell workstations. Flow cytometry was used to detect cell cycle and apoptosis. Protein mass spectrometry was used to construct differentially expressed protein profiles between parental and drug-resistant cells and some resistance-related proteins were validated by real time fluorescence quantitative polymerase chain reaction (qRT-PCR) and Western blot.Results:Secondary drug-resistant H1975/OSI cell line were successfully established. Compared with the parental cells, the resistance index of H1975/OSI cells increased by 27.25 times ( P<0.01), the cell proliferation ability decreased but the apoptosis resistance increased ( P=0.01), and no new drug-resistance related gene mutation in H1975/OSI cells. Meanwhile, the differential protein expression profiles of H1975 and H1975/OSI cells were built, and 307 upregulated proteins and 295 down-regulated proteins were found in resistant cells. When fibroblast specific protein-1 (FSP1) gene with expression up-regulation was diturbed in H1975/OSI cells, the cell IC50 value of osimertinib decreased 3.51 times ( P=0.02) , and when FSP1 was overexpressed in the H1975 cells, the IC50 value of osimertinib increased by 3.75 times ( P<0.01). Conclusions:We successfully established human NSCLC osimitinib-resistant cell line H1975/OSI. Protein differential expression profiles between H1975 and H1975/OSI was constructed successfully. It was found that FSP1 was involved in mediating the resistance of H1975/OSI to osimertinib.

Objective To study the mechanical properties and biological characteristics of 3D-printed porous β-tricalcium phosphate ［β-Ca3(PO4)2, β-TCP］ scaffolds, so as to provide guidance for the design of composite scaffolds in animal experimentation. Methods Poly 1,8-octanediol citrate (POC), a kind of novel biodegradable materials, was used as the adhesive. The 3D-printed porous β-TCP scaffolds were fabricated by fused deposition modeling (FDM) technology, and Gly-Arg-Gly-Asp-Ser (GRGDS), a kind of polypeptides, was added into the scaffolds to improve the adhesive property of cells. The optical microscope and scanning electron microscope (SEM) were used to observe the micro-pore architectures of those scaffolds. The material testing machine was used to conduct compressive test on the scaffolds, and the water contact angles of the scaffolds were measured. The cell adhesion rate and proliferation rate of the scaffolds were also tested by in vitro cell experiment. The model of SD rat skull defects was repaired by the scaffolds, and the osteogenic ability in vivo was further studied. Results The GRGDS, remaining active, was evenly distributed in the composite scaffolds. The micro-pore architectures of the polypeptide modified scaffolds changed, with improvement in cell adhesion rate, while the compressive modulus, water contact angle and osteogenic ability in vivo of the scaffolds were not obviously affected. Conclusions The cell adhesion capacity of β-TCP composite scaffolds modified by polypeptide improved significantly, while the mechanical properties and hydrophilicity, osteogenic ability in vivo of the scaffolds were not affected very much. These research results provide new ideas for reconstruction of scaffolds for repairing bone defects in clinic, and a laboratory basis for further clinical application of this scaffold.