BACKGROUND:Bone defects can directly affect the success rate and long-term stability of dental implants.Studies have shown that salidroside has the ability to promote the proliferation and differentiation of osteoblasts,but less is reported on its pathways related to osteogenic differentiation. OBJECTIVE:To investigate the effects of salidroside on the proliferation and differentiation of MC3T3-E1 cells and the expression of related genes and proteins through in vitro cell experiments. METHODS:Cell counting kit-8 test and alkaline phosphatase test were used to determine the optimal concentration of salidroside(0.5,1,5,10,and 50 μmol/L)in promoting the proliferation and differentiation of MC3T3-E1 cells.There were four groups in the experiment:control group,salidroside group,salidroside+LY294002 group,and LY294002 group,which were cultured with osteogenic induction solution,osteogenic induction solution containing 10 μmol/L salidroside,osteogenic induction solution containing 10 μmol/L salidroside+10 μmol/L LY294002,and osteogenic induction solution containing 10 μmol/L LY294002,respectively.The effects of salidroside and LY294002,an inhibitor of the PI3K/Akt signaling pathway,on the expressions of genes and proteins related to osteogenesis were observed. RESULTS AND CONCLUSION:Cell counting kit-8 assay and alkaline phosphatase assay showed that salidroside promoted the proliferation of MC3T3-E1 cells most significantly at 10 μmol/L.Compared with the control group,salidroside could promote mineralization,promote cell adhesion,reduce cell death,increase mRNA expression of Runx-2,osteocalcin and osteopontin(P<0.01),and increase protein expression of Runx-2 and p-Akt(P<0.01).However,the addition of LY294002 reversed the above results.These findings indicate that salidroside can promote the mineralization of MC3T3-E1 cells and the expression of osteogenesis-related genes and proteins,which may be related to the activation of PI3K/Akt signaling pathway.

Objective To analyze the proportion and clinicopathological characteristics of HER2-positive breast cancer patients with BRCA1/2 pathogenic variants, and their response to neoadjuvant anti-HER2 targeted therapy. Methods The clinicopathological data of 531 breast cancer patients with germline BRCA1/2 pathogenic variants (201 with BRCA1 variants and 330 with BRCA2 variants) were analyzed. Results Among the 201 BRCA1 and 330 BRCA2 variants, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared with BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients did not present any significant differences in clinicopathological features; however, compared with triple-negative breast cancer patients, HER2-positive patients had a later onset age and lower tumor grade. Among the 17 patients who received neoadjuvant anti-HER2 targeted therapy, 10 cases achieved pCR (58.8%), whereas 7 cases did not (41.2%). Conclusion HER2-positive breast cancer accounts for more than 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy. This phenomenon highlights the possibility of combining anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.

Objective To explore the correlation between neutrophil-to-lymphocyte ratio(NLR)and Behcet's disease(BD)activity.Methods A total of 103 BD patients were divided into the low activity group(0-4,61 cases)and the high activity group(5-11,42 cases)according to electronic medical record-based disease activity index(EMRAI)score.The white blood cell(WBC),neutrophil(NEU),lymphocyte(LY),platelet(PLT),red blood cell(RBC),hemoglobin(Hb),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IgG,IgA,IgM,complement C3 and C4 were detected.NLR and platelet-to-lymphocyte ratio(PLR)were calculated.The correlation between NLR,PLR and ESR,CRP,EMRAI were analyzed.Logistic regression was used to analyze the influencing factors of BD disease activity.Receiver operating characteristic(ROC)curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity.Results WBC,NEU,PLT,ESR,CRP,NLR,PLR,complement C3 and C4 in patients were higher in the high activity group than those in the low activity group(P＜0.05),and there were no significant differences in other indexes(P＞0.05).NLR was positively correlated with ESR,CRP and EMRAI in the whole group,while PLR was positively correlated with ESR,CRP and EMRAI in the whole group(P＜0.05).Logistic regression analysis showed that high NLR was a risk factor for BD disease activity(OR=1.511,95%CI:1.080-2.113,P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of NLR in evaluating BD disease activity was 0.706(95%CI:0.603-0.809).Conclusion NLR is effective in judging the disease activity of BD patients,and can be used as a biological index to evaluate the disease activity of BD.

BACKGROUND:Shikonin contributes to the promotion of bone defect repair and the treatment of osteoporosis. OBJECTIVE:To summarize the application potential of shikonin and its derivatives in oral soft and hard tissue regeneration. METHODS:A literature review was conducted in databases such as PubMed,Web of Science,Wanfang,China National Knowledge Infrastructure(CNKI),and VIP,spanning articles from 2002 to 2023.The search terms were"shikonin,oral cavity,periodontitis,antibacterial,bone formation,osteoclast,osteoporosis,toxicology"in Chinese and English. RESULTS AND CONCLUSION:Shikonin and its derivatives possess anti-inflammatory effects,inhibit periodontal pathogens such as Porphyromonas gingivalis,promote periodontal wound healing,and regenerate alveolar bone tissue.Shikonin formulations can be used to treat oral diseases such as aphthous ulcers and oral candidiasis.These findings suggest a promising future for shikonin and its derivatives in treating periodontal diseases,preventing oral ailments,and promoting the regeneration of both soft and hard periodontal tissues.Further research is needed to explore how to combine shikonin with tissue engineering to achieve quicker healing of oral soft and hard tissues.

To develop a traditional Chinese medicine （TCM） diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation， and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated， and 312 valid clinical case information collection forms were obtained， which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods， namely， differentiation analysis， Cronbach's coefficient， correlation coefficient， and stepwise regression， were used to screen out the candidate items， and Logistic regression analysis and factor analysis were used to assign weights to the items， and the final diagnostic model was determined by the receiver operating characteristic （ROC） curve， and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items： turbid dirt coating （with a weight value of 23， the same below）， sticky stools （16）， fullness in the epigastrium and abdomen （12）， dark complexion （12）， irritability （11）， brown spots on the skin （11）， heaviness of head （10）， and chest stuffiness （5）， and the degree score was 0， 0.5， 1.0， and 1.5 points corresponding to no， mild， moderate and severe symptoms， respectively. The total score was the sum of the degree score multiplied by the weighted value of each item， and when the total score reached 33 points， it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group， and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%， with the specificity of 95.90% and 89.74%， the Yoden index of 0.85 and 0.79， the positive predictive value of 95.28% and 89.47%， the negative predictive value of 90.70% and 89.74%， the diagnostic advantage ratios of 198.18 and 72.67， and the Kappa values of 0.86 and 0.79， which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.

Objective:To analyze the changes of fasting plasma glucose(FPG)level before and after menopause.Methods:Kailuan health checkup cohort was used to extract data of women aged≥18 years who participated in the first physical examination of Kailuan physical examination cohort and had menopausal age at the end of the seventh physical examination. A total of 3 749 women with 22 057 physical examination records were included in the analysis. Natural logarithmic transformation was applied to FPG, and a segmented linear mixed-effects model was used to analyze the changes in ln-transformed FPG before and after menopause. Additionally, an interaction analysis was performed to assess the multiplicative effect of baseline age and baseline body mass index(BMI)on ln-transformed FPG concerning pre- and post-menopausal periods.Results:The average age of the first physical examination for women in this study was (45.63±4.52)years, the median menopausal age was 51(50~53)years, and the median number of physical examinations was 6(5~7)times. The results of the piecewise linear mixed effect model showed that lnFPG increased from 1 year before menopause, with an average annual increase of 0.021 mmol/L, and continued to increase from menopause to 5 years after menopause, with an average annual increase of 0.007 mmol/L. LnFPG tended to be stable after 5 years of menopause. Baseline age could affect the changes of lnFPG before and after menopause, and there was a negative multiplicative interaction between baseline age ≥45 years and the time period from 6 years to 1 year before menopause( P=0.032). Women with baseline age ≥45 years had a higher average annual increase in lnFPG from 1 year before menopause to 5 years after menopause than women with baseline age <45 years( P<0.05). On lnFPG, there was a positive multiplicative interaction between baseline BMI and time segments around menopause. Compared to women with BMI <24.0 kg/m 2, obese women displayed more annual increase in lnFPG from 6 years to 1 year before menopause as well as from menopause to 5 years after menopause( P<0.05). Conclusions:Menopause has an adverse impact on FPG, with the most significant changes occurring within the period of one year before menopause and up to five years after menopause. Age and BMI significantly influence the changes in FPG before and after menopause.

Objective To investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer.Methods A total of 48 BRCA mutation carriers(16 with BRCA1 and 32 with BRCA2)and 78 age-matched non-carriers were included in this study.Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues.The FOXP3 RNA expression in 39 BRCA1,36 BRCA2,and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombin-ation deficiency scores were evaluated to validate the immunohistochemistry results.Results The FOXP3 positive rate was 43.8%(7/16)in BRCA1 mutation carriers,59.4%(19/32)in BRCA2 mutation carriers,and 9.0%(7/78)in non-carriers.The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers(P=0.002;P<0.001).TCGA-BRCA results showed that the FOXP3 RNA level in BRCA1/2 mutant breast cancer was significantly higher than that in non-carriers(P=0.02,P=0.004).The FOXP3 RNA level was positively correlated with the homologous recombination deficiency score(Spearman R=0.30,P<2.2e-16).Conclusion Patients with BRCA1/2 mutant breast cancers have higher FOXP3expression than non-carriers,and may be more sensitive to immunotherapy.

Objective To optimize the preparation process of Swertia patens,Burk.standard decoction and establish its quality standard by using the quality by design(QbD)concept.Methods Critical Quality Attributes(CQAs)were predicted and analyzed according to the quality marker(Q-marker)theory of traditional Chinese medicine;Failure mode and effects analysis(FMEA)was used to screen critical process parameters(CPPs);The measurement method of key quality attributes was established;The extraction process was optimized by Box Behnken test after the preliminary range was determined according to the single factor test;The entropy method was used for comprehensive scoring;The design space was established and the optimal operation space for process validation was selected;Standard decoction of Swertia patens Burk in fifteen batches with different habitats were prepared with the best technology,and the quality standards for the extraction rate,extract,thin layer chromatography,fingerprint,content,and the content transfer rate were established finally.Results The key quality attributes were swertiamarin content,gentiopicrin content,and paste yield;The key process parameters were soaking time,water amount,and decocting time;The established model had statistical significance;The optimum conditions were as follows:soaking time 90 min,adding water 15 times,decocting time 30 min(second decocting 20 min);The paste yield was 21.13％-30.73％;The extract was 82.00％-88.00％;The spot of swertiamarin was clear in TLC;The similarity between each samples in 15 batches and reference atlas were＞0.85％;The content of swertiamarin was 250.64-385.21 mg·g-1,and the transfer rate was 43.76％-77.73％;The content of gentiopicrin was 0.69-2.70 mg·g-1,and the transfer rate was 56.02％-105.29％.Conclusion Based on the above methods and techniques,the preparation process of Swertia patens Burk.The standard decoction was screened,which provides a reference for the preparation development and quality control of its formula granules.

Objective:To evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM).Methods:A retrospective cohort study design was performed . Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease, Children′s Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions:The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Objective:To explore the curative effect and prognostic assessment value of percutaneous kyphoplasty(PKP)in treating osteoporosis-caused spinal vertebral compression fractures by using imaging parameters of pelvic sagittal X-ray.Methods:A total of 198 patients with osteoporosis-caused spinal vertebral compression fractures who received treatment from January 2022 to January 2023 were selected,and they were divided into effective group(171 cases)and ineffective group(27 cases)according to the treatment effect.All patients underwent PKP treatment,and the parameters of preoperative measurements included sagittal vertical axis(SVA)of cervical vertebra 7(C7),the thoracic vertebra 1 pelvic angle(T1PA),thoracic kyphosis(TK),lumbar lordosis(LL)and sacral slope(SS).The clinically curative effect and prognosis between two groups were compared.Results:After PKP treatment,49 cases of 198 patients were cured,and 69 cases appeared significant effect,and 53 cases were effective,and 27 cases were ineffective.The SVA,LL and SS levels of effective group were significantly lower than those of ineffective group,and the differences of them were statistically significant(t=6.485,3.250,2.325,P<0.05),and the T1PA and TK of the effective group were significantly higher than those of the ineffective group(t=2.387,3.245,P<0.05),respectively.In 198 patients,39 cases occurred postoperative complications(20 cases occurred bone cement leakage,and 15 cases occurred recurrent adjacent vertebral fracture,and 2 cases occurred pulmonary embolism,and 2 cases occurred others),and 159 cases did not occurred complications.The SVA,LL and SS levels in patients without complications were significantly lower than those in patients with complications(t=10.304,5.669,0.844,P<0.05),and the T1PA and TK of patients without complications were significantly higher than those of patients with complications,and the differences were significant(t=3.494,5.550,P<0.05),respectively.The results of receiver operating characteristic(ROC)curve analysis showed that SVA,T1PA,TK,LL and SS had a certain value in assessing the curative effect and prognosis of PKP in treating osteoporosis-caused spinal vertebral compression fractures.Conclusion:Preoperative detection of imaging parameters of pelvic sagittal X-ray can assess the curative effect and prognosis of osteoporosis-caused spinal vertebral compression fractures,which can provide a certain reference for clinical treatment.