ObjectiveTo explore the possible mechanism of Osteoking （OK） on postmenopausal osteoporosis （PMOP）. MethodForty adult female mice were randomly divided into a sham operation （Sham） group， osteoporosis model （OVX） group， estradiol intervention （E₂） group， and OK group， with 10 mice in each group. The modeling was completed by conventional back double incision ovariectomy， and the corresponding drugs were given one week later. After 12 weeks， the body mass and uterine index of mice were measured， and the pathological changes of bone tissue and the number of osteoclasts （OCs） were determined by hematoxylin-eosin （HE） and tartrate-resistant acid phosphatase （TRAP） staining， respectively. Bone mineral density （BMD）， trabecular number （Tb.N）， trabecular separation （Tb.Sp）， and bone volume fraction （BV/TV） were measured by microcomputed tomography （Micro-CT）. The maximum load of the femur was detected by a three-point bending test. The contents of tumor necrosis factor-α （TNF-α） and bone resorption marker C-terminal telopeptide of type Ⅰ collagen （CTX-1） were measured by enzyme linked immunosorbent assay （ELISA）. The protein expression levels of nuclear factor-kappa B p65 （NF-κB p65）， phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65）， nuclear factor kappa B inhibitor alpha （IκBα）， phosphorylated nuclear factor kappa B alpha （p-IκBα）， nuclear factor of activated T cells 1 （NFATc1）， and proto-oncogene （c-Fos） were detected by Western blot. The mRNA expressions of OCs-related specific genes matrix metalloproteinase-9 （MMP-9）， NFATc1， TRAP， cathepsin K （CTSK）， and c-Fos were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the Sham group， the uterine index decreased significantly in the OVX group， and the body mass （BMI） increased significantly. The structure of bone trabeculae was completely damaged， and the number of OCs increased. BMD， Tb.N， BV/TV， and maximum load decreased， while Tb.Sp was up-regulated. The levels of TNF-α and CTX-1 in serum were up-regulated. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were increased. The mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were up-regulated （P<0.05， P<0.01）. Compared with the OVX group， the body mass of the OK and E₂ groups decreased， and the uterine index increased. The bone trabeculae increased， and the number of OCs decreased. BMD， Tb.N， BV/TV， and maximum load increased， while Tb.Sp decreased. The levels of TNF-α and CTX-1 in serum were decreased. The protein expressions of c-Fos， p-NF-κB p65/NF-κB p65， NFATc1， and p-IκBα/IκBα were decreased， and the mRNA expressions of NFATc1， c-Fos， CTSK， TRAP， and MMP-9 were decreased （P<0.05， P<0.01）. ConclusionOK can inhibit the NF-κB/NFATc1 signaling pathway and reduce bone mass loss by reducing the level of inflammatory injury factors in PMOP mice， which is one of the mechanisms for treating PMOP.

Objective: To explore the effects of protein powder on the bioavailability of perfluoroalkyl substances (PFASs) in blood and kidneys of rats and renal function change. Methods: Twenty-four rats of the SD strain were randomly divided into the negative control group, PFASs group and protein powder group, with 8 rats (half males and half females) in each group. PFASs included 13 perfluorocarboxylic acids (PFCAs) and 8 perfluorosulfonic acids (PFSAs), and the mixture was used as a test subject for intervention. The rats in the negative control group were given deionized water at doses of 20 mL/kg·bw, in the PFASs group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of deionized water, and in the protein powder group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of protein powder (0.258 g/mL). After intervention for 28 successive days, body weight and kidney mass were weighed, and the kidney volume index was calculated. Serum creatinine and blood urea nitrogen were detected by an automatic biochemical analyzer. The PFCAs, PFSAs and PFASs contents were quantified in blood and kidney using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry, and the bioavailability was estimated. Results: There was no significant differences in kidney mass, kidney volume index, serum creatinine and blood urea nitrogen among the negative control group, PFASs group and protein powder group (all P>0.05). The bioavailability of blood PFCAs, PFSAs and PFASs in the protein powder group was not significantly different from the PFASs group (all P>0.05). Compared with the PFASs group, the bioavailability of PFCAs, PFSAs and PFASs were significantly increased in kidneys of male rats in the protein powder group (all P<0.05), while were not significant different in those of female rats (all P>0.05). Conclusion Protein powder at the dose of this study can significantly improve the bioavailability of PFASs in kidneys of male rats, while there no obvious effects on the bioavailability of blood PFASs and renal function.

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

italic>Salvia miltiorrhiza, a commonly used traditional Chinese medicine, has been widely recognized for its blood-activating and stasis-removing properties in the clinical treatment of cardiovascular and cerebrovascular diseases. The synthesis and regulatory mechanism of tanshinones, the key active constituents of Salvia miltiorrhiza, have been a hot topic of research. The paper summarized the research findings on the regulation of tanshinone biosynthesis by transcription factors such as AP2/ERF, bHLH, MYB, bZIP, and WRKY in recent years. The review identifies the existing issues in the transcriptional regulation studies of Salvia miltiorrhiza and discusses the research direction of transcription factors in the regulation of tanshinone biosynthesis, providing a theoretical basis for the further discovery and utilization of functional genes involved in the regulation of tanshinone bioactive constituents.

Objective To investigate the effects of 3-Butylphthalideon oxidative stress-induced apoptosis of neuronal cells PC-12 and its mechanism.Methods PC-12 cells were divided into four groups,Vector group:DMSO treated and transfected with vector plasmid;3-butylphthalide+vector group:DMSO+25 μmol·L-1 3-butylphthalidewas treated with vector plasmid was transfected;PRDM5 group:PR domain zinc finger protein 5(PRDM5)overexpression plasmid was transfected with DMSO;3-butylphthalide+PRDM5 group:Treated with DMSO+25 μmol·L-1 3-butylphthalide and transfected with PRDM5 overexpression plasmid.Apoptosis levels of neurons were detected by flow cytometry;Cleaved cysteine aspartate proteinase 3(Cleaved-caspase 3),B cell lymphoma-2(Bcl-2)and Bcl-2 associated X(Bax)expression levels were detected by Western blotting;binding sites of 3-Butylphthalideand PRDM5 were analyzed by molecular docking.Results The apoptosis levels of vector group,3-butylphthalide+vector group,PRDM5 group and 3-butylphthalide+PRDM5 group were(63.52±5.72)％,(20.48±3.56)％,(79.48±8.13)％and(22.58±3.01)％;Cleaved-caspase 3 expression levels were 0.89±0.09,0.29±0.03,1.12±0.09 and 0.31±0.05;the expression levels of Bcl-2 were 0.31±0.02,0.79±0.05,0.12±0.01 and 0.89±0.11;the expression levels of Bax were 0.83±0.08,0.25±0.03,1.03±0.11 and 0.27±0.03,respectively.The above indexes of Vector group were significantly different from those of PRDM5 group(all P＜0.05).That 3-Butylphthalidewas bound to PRDM5(free energy-12.55 kcal·mol-1),and binding sites were K413R and D414A.Conclusion 3-butylphthalidebinds to K413R and D414A of PRDM5,inhibiting the function of PRDM5 and improving the apoptosis of neuronal cells induced by oxidative stress.

Objective To evaluate the bioequivalence and safety of the test formulation dapagliflozin tablets(10 mg)compared to the reference formulation in healthy adult subjects under fasting and fed conditions.Methods A single-center,randomized,open-label,two-period,two-sequence,crossover study design was employed.A total of 68 subjects were enrolled,with 32 subjects in the fasting group and 36 subjects in the fed group.Each subject received a single oral dose of either the test or reference formulation 10 mg.Plasma concentrations of dapagliflozin were measured using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.2 to assess the bioequivalence of the two formulations and their safety.Results Key pharmacokinetic parameters of the test and reference formulations in the fasting group were as follows:Cmax were(195.08±58.24)and(200.22±45.20)ng·mL-1;tmax were 0.67 and 0.67 h;AUC0_t were(553.52±97.82)and(552.47±106.07)ng·h·mL-1;AUC0-∞ were(580.40±103.79)and(579.42±111.23)ng·h·mL-1.In the fed group,the parameters were:Cmax were(123.38±39.50)and(125.80±39.05)ng·mL-1;tmaxwere 2.00 and 2.50 h;AUC0-t were(606.05±129.44)and(596.73±131.97)ng·h·mL-1;AUC0-∞ were(637.12±138.77)and(629.38±136.81)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ for the test and reference formulations were within the bioequivalence range of 80.00％to 125.00％.The incidence of adverse drug events was 3.23％in the fasting group and 5.56％in the fed group.Conclusion The test formulation of dapagliflozin tablets is bioequivalent to the reference formulation in healthy Chinese subjects and has a good safety profile.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

The quality of Japanese forensic experts has been widely recognized around the world,which cannot be separated from the "ripple effect" caused by the rapid rise of the modern forensic edu-cation in Japan.By continuously adopting foreign forensic education resources and teaching experience,it has finally formed a forensic professional talent training model with a clear hierarchy of basic educa-tion and professional training,as well as classroom teaching and case studies complementing each other;and it continuously improves the comprehensive quality of practitioners through domestic training and international exchange and cooperation,providing talented professionals for the development of the Japanese forensic industry.In this context,this article takes the development history of Japanese foren-sic medicine as the starting point to study how it gradually formed the embryonic form of forensic education in modern times.Based on this,it analyzes the characteristics of Japan's modern forensic medicine talent training model,summarizes excellent experiences for localized transformation,such as emphasizing the role of practical teaching,exerting the effectiveness of vocational skills training,and promoting international exchange and cooperation,to provide reference and inspiration for the training of relevant professional talents in China.

Objective:To explore the mechanism of long non-coding RNA RP11-79H23.3 in the development and progression of prostate cancer.Methods:The lnCAR database was used to analyze the RP11-79H23.3 content in prostate cancer tissues and adjacent tissues. RP11-79H23.3 content in prostate cancer cell lines C4-2B, LNCaP, DU-145, and 22Rv1 was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Taking 22Rv1 as the research target, colony formation experiments and scratch experiments were used to detect the effects of overexpression of RP11-79H23.3 on the proliferation and migration of 22Rv1 cells. The LncRNome and lncACTdb databases were used to predict the downstream gene and binding sequences of RP11-79H23.3. The Cancer Genome Atlas (TCGA) database was used to analyze the correlation between RP11-79H23.3 and miR-410 expression in prostate cancer tissues. The binding of RP11-79H23.3 and miR-410 was confirmed by dual-luciferase reporter gene experiment. The effect of RP11-79H23.3 on the expression of miR-410 was detected by RT-qPCR. Western blotting was used to detect the effect of RP11-79H23.3 on the expression of phosphatase and tensin homolog/protein kinase B/mammalian target of rapamycin (PTEN/AKT/mTOR) signaling pathway proteins in 22Rv1 cells. The measurement data were expressed as mean ± standard deviation ( ± s), paired sample t-test was used for comparison between two groups, and one-way analysis of variance was used for comparison between multiple groups. Results:Compared with adjacent tissues, RP11-79H23.3 was lowly expressed in prostate cancer tissues ( P<0.01). Compared with normal prostate epithelial cells RWPE-1, RP11-79H23.3 was lowly expressed in prostate cancer cell lines C4-2B, LNCaP, DU-145, and 22Rv1 ( P<0.05). The expression of RP11-79H23.3 in 22Rv1 cells in the control group and RP11-79H23.3 group were 1.02 ± 0.30 and 8.94±1.95, respectively. 22Rv1 cells were successfully overexpressed RP11-79H23.3 compared with the control group ( t=4.04, P<0.01). The number of 22Rv1 cell clones in the control group and RP11-79H23.3 group were 166.10 ± 18.35 and 35.03±6.98, respectively. Overexpression of RP11-79H23.3 could inhibit the proliferation of 22Rv1 cells compared with the control group ( t=6.67, P<0.01). The migration rates of 22Rv1 cells in the control group and RP11-79H23.3 group were (67.40 ± 6.29)% and (26.42 ± 6.24)%, respectively. Overexpression of RP11-79H23.3 could inhibit the migration of 22Rv1 cells compared with the control group ( t=5.71, P<0.01) .Dual-luciferase reporter gene experiment showed that RP11-79H23.3 directly binds to miR-410 ( t=6.20, P<0.01). The expression of miR-410 in 22Rv1 cells in the control group and RP11-79H23.3 group were 6.22±1.39 and 1.05±0.23, respectively. RP11-79H23.3 could inhibit the expression of miR-410 in 22Rv1 cells compared with the control group ( t=3.68, P<0.01). At the same time, RP11-79H23.3 can inhibit the transduction of the PTEN/AKT/mTOR signaling pathway in 22Rv1 cells. Conclusion:RP11-79H23.3 blocks the PTEN/AKT/mTOR signaling pathway by inhibiting the expression of miR-410, thereby inhibiting the proliferation and migration of prostate cancer 22Rv1 cells.

Objective To investigate the effect of Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the changes of gastric mucosal pathological score and gastrointestinal hormones in patients with chronic atrophic gastritis(CAG)of liver stagnation and spleen deficiency type.Methods A total of 156 cases of CAG patients with liver stagnation and spleen deficiency syndrome were randomly divided into a control group and an observation group,78 cases in each group.The control group was treated with conventional western medicine,and the observation group was treated with Xiao Chaihu Decoction and Xiangsha Liujunzi Decoction on the basis of treatment for the control group.The course of treatment covered four weeks.The changes in the scores of traditional Chinese medicine(TCM)symptoms such as epigastric distention and pain,poor appetite,loose stools,limb weakness,belching and acid regurgitation,gastric mucosal pathological scores and serum levels of gastrointestinal hormones of motilin(MTL)and gastrin(GAS)in the two groups were observed before and after treatment.The negative conversion rate of Helicobacter pylori(Hp)in the two groups was compared,and the clinical efficacy and safety of the two groups were evaluated.Results(1)After four weeks of treatment,the total effective rate of the observation group was 93.59％(73/78),which was significantly higher than 82.05％(64/78)of the control group,and the difference between the two groups was statistically significant(P＜0.05).(2)After treatment,the scores of TCM symptoms such as epigastric distention and pain,poor appetite,loose stool,limb weakness,belching and acid regurgitation in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease in the observation group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the pathological scores of gastric mucosa in the two groups were significantly decreased when compared with those before treatment(P＜0.05),and the decrease in the observation group was more significant than that in the control group(P＜0.01).(4)After four weeks of treatment,the negative conversion rate of Hp in the observation group was 91.03％(71/78),which was significantly higher than that in the control group(75.64％,59/78),and the difference between the two groups was statistically significant(P＜0.05).(5)After treatment,the level of serum GAS in the two groups was significantly decreased(P＜0.05)and the serum MTL level was significantly increased compared with that before treatment(P＜0.05);the decrease of serum GAS level and the increase of serum MTL level in the observation group were significantly superior to those in the control group(P＜0.05).(6)There were no obvious abnormalities in the routine test of blood,urine,stool,kidney function,and liver function,electrocardiograph and other safety indicators during the treatment of the two groups of patients,no adverse reactions such as dizziness,rash and chest distress occurred either,with high safety.Conclusion Xiao Chaihu Decoction combined with Xiangsha Liujunzi Decoction exerts a significant therapeutic effect on GAS of liver stagnation and spleen deficiency type,which can effectively relieve the clinical symptoms,improve the pathological changes of gastric mucosa and promote Hp negative conversion.The therapeutic mechanism may be related to the regulation of gastrointestinal hormone levels.