BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

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 investigate the protective effect and mechanisms of total alkaloids of Bulbus Fritillaria Pallidiflora (TA-BFP) on pulmonary fibrosis in silicosis mice. Methods i) Bulbus Fritillaria Pallidiflora (BFP) powder was collected by heating and refluxing twice with 70.00% ethanol, and the dried concentrated sample was purified using cation-exchange and macroporous adsorbent resins to obtain TA-BFP. The total alkaloids level was detected using ultraviolet spectrophotometry and the characteristic peaks in TA-BFP were identified using the high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD). ii) Specific pathogen-free male C57BL/6J mice were randomly divided into the control group, model group and intervention group, with 15 mice in each group. Mice in the model group and the intervention group were treated with 80 μL silica suspension with a mass concentration of 62.5 g/L, while the control group was treated with an equal volume of 0.9% sodium chloride solution using non-exposed tracheal instillation method. On the 28th day after modeling, mice in the intervention group were given TA-BFP at a dose of 60 mg/kg body mass, and the model group and control group were given 2.00% Tween-80 solution at the same volume by gastric gavage, once per day, for 28 days. The mouse lung tissue pathology was observed, lung organ coefficient was calculated, and inflammation and fibrosis scores were assessed after the intervention period. Serum levels of mouse interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay. Results i) The total alkaloid level of TA-BFP in the BFP powder was 50.36% after elution and purification. A total of nine alkaloid components in TA-BFP were identified by HPLC-ELSD. ii) The results of lung histopathology showed that no obvious changes of inflammation and fibrosis were identified in the lungs of mice in the control group, obvious changes of inflammation and fibrosis were identified in the lungs of mice in the model group, and the intervention group showed reduced inflammation and fibrosis in the lungs of mice compared with that of the model group. The lung organ coefficient, pulmonary inflammation score, pulmonary fibrosis score, and levels of serum IL-1β, IL-6, and TNF-α were significantly higher in the model group than those in the control group (all P<0.05). The lung organ coefficient, pulmonary inflammation score, pulmonary fibrosis score, and levels of serum IL-1β, and TNF-α were significantly higher in the intervention group than those in the control group (all P<0.05), while the pulmonary inflammation score, pulmonary fibrosis score, and levels of serum IL-1β, IL-6, and TNF-α were significantly lower in the intervention group than those in the model group (all P<0.05). Conclusion TA-BFP alleviates pulmonary inflammation in silicosis mice, thereby delaying the progression of pulmonary fibrosis. The mechanism may involve in inhibiting the expression of inflammatory factors IL-1β, IL-6, and TNF-α.

Saponins associated with Panax notoginseng (P. notoginseng) demonstrate significant therapeutic efficacy across multiple diseases. However, certain high-yield saponins face limited clinical applications due to their reduced pharmacological efficacy. This study synthesized and evaluated 36 saponin-1,2,3-triazole derivatives of ginsenosides Rg1/Rb1 and notoginsenoside R1 for anti-adipogenesis activity in vitro. The research revealed that the ginsenosides Rg1-1,2,3-triazole derivative a17 demonstrates superior adipogenesis inhibitory effects. Structure-activity relationships (SARs) analysis indicates that incorporating an amidyl-substituted 1,2,3-triazole into the saponin side chain via Click reaction enhances anti-adipogenesis activity. Additionally, several other derivatives exhibit general adipogenesis inhibition. Compound a17 demonstrated enhanced potency compared to the parent ginsenoside Rg1. Mechanistic investigations revealed that a17 exhibits dose-dependent inhibition of adipogenesis in vitro, accompanied by decreased expression of preadipocytes. Peroxisome proliferator-activated receptor γ (PPARγ), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4) adipogenesis regulators. These findings establish the ginsenoside Rg1-1,2,3-triazole derivative a17 as a promising adipocyte differentiation inhibitor and potential therapeutic agent for obesity and associated metabolic disorders. This research provides a foundation for developing effective therapeutic approaches for various metabolic syndromes.
Adipogenesis/drug effects* ; Triazoles/chemical synthesis* ; Ginsenosides/chemical synthesis* ; Saponins/chemical synthesis* ; Animals ; Mice ; Structure-Activity Relationship ; PPAR gamma/genetics* ; 3T3-L1 Cells ; Adipocytes/metabolism* ; Panax notoginseng/chemistry* ; Drug Design ; Molecular Structure ; Humans ; Cell Differentiation/drug effects* ; Fatty Acid-Binding Proteins/genetics*

Objective:To explore the therapeutic efficacy and prognostic factors of combined rituximab and intensive chemotherapy for sporadic adult Burkitt lymphoma (BL) .Methods:This retrospective study examined the clinical and survival data of 30 patients newly diagnosed with BL between July 2011 and February 2023 at the Blood Diseases Hospital. Kaplan-Meier method was used for survival analysis, and the log-rank test was used for univariate analysis of prognostic factors.Results:The median age of the 30 patients was 43 years (24 - 66 years), and the male to female ratio was 3: 2. Extranodal invasion was present in 80% of the patients, with involvement of the bone marrow in 53.3% and central nervous system in 10.0%. The Ann Arbor stage was Ⅲ and Ⅳ in 86.7%. According to the number of Burkitt Lymphoma International Prognostic Index (BL-IPI) risk factors, patients were classified as low risk (0) in 20.0%, intermediate risk (1) in 43.3%, and high risk (≥2) in 36.7%. All patients were treated with an induction regimen of rituximab combined with intensive chemotherapy, with objective and complete response rates of 80.0% and 76.7%, respectively. The median follow-up was 49 months (6-153 months), and the 5-year progression-free survival (PFS) and overall survival (OS) rates were both (76.7±7.7) %. All patients with limited stage ( n=4) achieved continuous complete remission (CCR). Patients who had high risk, advanced stage sensitive to induction therapy ( n=10) sequentially received first-line autologous hematopoietic stem cell transplantation (auto-HSCT) as consolidation therapy; 9 patients achieved CCR, whereas 1 patient with central nervous system invasion developed early disease progression and died. The BL-IPI low, intermediate, and high risk groups had respective 5-year PFS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0069) and OS rates of (83.3±15.2) %, 100.0%, and (45.5±15.0) % ( P=0.0075). The main adverse effects of induction therapy were myelosuppression and secondary infections, which were effectively managed by appropriate symptomatic treatment. Univariate analysis demonstrated that worse PFS was associated with BL-IPI score ≥2 ( HR=4.90, 95% CI 1.02-23.45, P=0.0329) ; extranodal invasion at ≥2 sites ( HR=12.62, 95% CI 2.59-61.62, P=0.0021) ; and failure to achieve first complete response (CR1) after induction therapy ( HR=31.86, 95% CI 4.19-242.20, P<0.0001) . Conclusions:Intensive immunochemotherapy regimens were effective and well-tolerated by adult patients with highly aggressive BL. Treatment efficacy was ideal in patients with limited-stage disease, whereas prognosis was unsatisfactory in patients with high-risk BL-IPI. Sequential first-line auto-HSCT consolidation therapy may further improve outcomes in patients with high-risk advanced-stage disease who are sensitive to induction therapy. BL-IPI score ≥2, extranodal invasion at ≥2 sites, and failure to achieve CR1 after induction therapy were adverse prognostic factors in adult patients with BL.

Objective:To explore the gait and eye movement parameters in early Parkinson's disease(PD)with sleep disorders, and analyze their association with underlying pathophysiological mechanisms.Methods:This study was a cross-sectional single-center design that included 82 early PD patients with Hoehn-Yahr(H-Y)staging ≤2.5 who visited Beijing Hospital from October 2023 to May 2025.Patients were divided into two groups according to the PDSS-2 score(total score ≤15 for the no sleep disorder group and total score >15 for the sleep disorder group). Gait and eye movement parameters were collected respectively through the ReadyGo system and the EyeKnow eye movement system, and analyzed in combination with clinical scales.Multivariate logistic regression was employed to identify independent characteristic parameters associated with sleep disorders.Results:In terms of gait, the sleep disorder group had significantly lower step speed, left-right stride speed, and left-right swing speed(all P<0.05), and significantly higher variability of left-right stride time( P=0.017, 0.026). Regarding eye movements, the sleep disorder group had significantly more vertical smooth pursuit offsets[(56.24±2.87)times vs.(45.98±18.18)times, P=0.040], significantly higher maximum real-time variability of the right eye in response to light stimuli(90.75 vs.67.95%, P=0.006), and a longer latency to error responses in the counter-scanning task(337.06 vs.286.63 ms, P=0.005). To precisely control for confounding factors, key covariates such as mood and disease severity were included in the multivariate logistic regression model.After comprehensive adjustment, higher anxiety levels(Hamilton Anxiety Rating Scale, HAMA)( OR=1.32, P<0.001)and an increased number of vertical smooth pursuit offsets( OR=1.06, P=0.010)were independent factors associated with sleep disorders in early PD patients. Conclusions:In early PD patients, sleep disorders are closely associated with specific abnormalities in gait and eye movement parameters.In particular, vertical smooth pursuit offsets may serve as an objective biomarker independent of emotional status, reflecting the dysfunction of shared neural circuits.However, further mechanism studies are needed to verify whether they reflect the dysfunction of shared neural circuits.

Objective:To evaluate gait characteristics in early-stage Parkinson′s disease (PD) patients using an artificial intelligence-based quantitative motor function assessment system (Readygo) and validate whether PD patients with clinically normal gait actually exhibit objective gait impairments, and to explore the features and progression patterns of gait dysfunction in early PD.Methods:This cross-sectional, single-center study enrolled early-stage PD patients (Hoehn-Yahr stage≤2.5) from outpatient or inpatient departments of Beijing Hospital between October 2023 and October 2024, along with accompanying caregivers as healthy controls (HCs). Demographic data (sex, age, education level) were collected, and cognitive, psychological, and sleep-related scales assessments were administered. Based on the gait score (Item 3.10) from the Movement Disorder Society-Unified Parkinson′s Disease Rating Scale-Ⅲ (MDS-UPDRS-Ⅲ), PD patients were stratified into 3 subgroups: PD-normal gait (score=0), PD-mild gait impairment (score=1), and PD-moderate gait impairment (score=2). The Readygo system quantified gait parameters, including step width, stride length, step height, gait speed, stride velocity, swing velocity, and turn duration. Binary Logistic regression was uesd to identify biomarkers differentiating PD-normal gait group from HCs.Results:A total of 66 early-stage PD patients and 34 HCs were enrolled. Across the HCs, PD-normal gait, PD-mild gait impairment and PD-moderate gait impairment groups, there was a progressive decline in gait speed [1.07 (0.97, 1.15) m/s vs 0.97 (0.90, 1.06) m/s vs 0.90 (0.82, 1.00) m/s vs 0.77 (0.72, 0.86) m/s, H=29.949, P<0.001], bilateral stride velocity [left: 1.14 (1.07, 1.21) m/s vs 1.06 (0.94, 1.14) m/s vs 0.95 (0.88, 1.04) m/s vs 0.86 (0.76, 0.93) m/s, H=30.778, P<0.001; right: 1.12 (1.04, 1.22) m/s vs 1.04 (0.95, 1.13) m/s vs 0.96 (0.90, 1.04) m/s vs 0.89 (0.77, 0.90) m/s, H=29.561, P<0.001], and bilateral swing velocity [left: (2.56±0.28) m/s vs (2.38±0.32) m/s vs (2.19±0.33) m/s vs (1.96±0.32) m/s, F=14.132, P<0.001; right: 2.46 (2.35, 2.62) m/s vs 2.35 (2.13, 2.62) m/s vs 2.22 (2.05, 2.36) m/s vs 2.03 (1.71, 2.13) m/s, H=25.771, P<0.001], along with a progressive shortening of bilateral step length [left: 1.19 (1.14, 1.27) m vs 1.15 (1.04, 1.22) m vs 1.05 (0.93, 1.18) m vs 0.95 (0.80, 1.06) m, H=32.613, P<0.001; right: 1.20 (1.14, 1.30) m vs 1.13 (1.03, 1.22) m vs 1.07 (0.90, 1.17) m vs 0.97 (0.80, 1.03) m, H=30.528, P<0.001]. Conversely, turning time progressively lengthened [1.20 (1.09, 1.49) s vs 1.21 (1.10, 1.46) s vs 1.30 (1.19, 1.51) s vs 1.98 (1.53, 2.12) s, H=23.195, P<0.001]. Logistic regression identified that the right stride length was a discriminative factor between HCs and PD-normal gait group ( OR=0.023, 95% CI 0-0.291, P=0.012). Conclusions:As gait dysfunction worsens, PD patients demonstrate gradual reductions in speed-related parameters and stride length, with increasing turn duration.Early PD patients with clinically normal gait may already exhibit subtle impairments. Right stride length may serve as a potential biomarker to distinguish PD patients from HCs.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.

Objective:To construct an evaluation system for the risk factors of PICC catheter malposition in patients with hematological diseases, providing a reference for the prevention of central venous access malposition in these patients.Methods:From July 2022, a literature review was conducted to retrieve literature published in database and website such as PubMed, Web of Science domestically and internationally related to the risk assessment system of PICC catheter malposition in hematology patients. After full-text screening and extraction, the articles were included in the system′s item pool. Through further discussions among the research group′s experts, in conjunction with evidence-based findings, the system′s consultation items were formulated. Using the Delphi expert consultation method, a standard for PICC catheter malposition risk assessment system applicable to hematology patients was ultimately formulated.Results:In this study, 25 experts were invited for consultation: 24 females and 1 male, with an average age of (48.36 ± 6.82) years. After two rounds of expert consultations and revisions, the risk factors for PICC catheter malposition in hematology patients were identified to include 4 first-level indicators: patient factors, treatment factors, catheter-related factors, and operational factors, along with 11 second-level indicators and 25 third-level indicators. The positive coefficients of the experts in the two rounds of consultations were 84% and 100%, respectively; the Kendall coordination coefficients were 0.22 and 0.55 (both P<0.05); and the expert authority coefficient was 0.93. Conclusions:The risk assessment scale for PICC catheter malposition in patients with hematological diseases has high expert recognition and good consistency, and has clinical practice and guiding value.

Objective To investigate the protective effects of Ligilactobacillus salivarius Li01(L.salivarius Li01)against DNA damage induced by Helicobacter pylori(Hp),Benzo(a)pyrene(BaP),and Hp+BaP,and to evaluate the probiotic properties of L.salivarius Li01.Methods After 1 week of adaptive feeding,specific pathogen-free male Mongolian gerbils were randomly assigned to groups and subjected to intragastric administration of Hp,BaP,and Hp+BaP for model induction.At week 32 post model establishment,therapeutic L.salivarius Li01 was administered intragastrically.At week 36,peripheral blood samples were collected from each group for the comet assay,while liver tissues were collected and tested for Cyp1a1 gene expression levels.Results Compared with those in the control group,the comet tail length,％tail DNA,and hepatic Cyp1a1 expression levels were significantly increased in the Hp,BaP,and Hp+BaP groups(P＜0.0001).Among these,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly higher in the Hp+BaP group than in the Hp and BaP groups(P＜0.05).Following intervention with L.salivarius Li01,the comet tail length,olive tail moment,％tail DNA,and hepatic Cyp1a1 expression levels were significantly reduced in each group(P＜0.001).Conclusions Hp infection,BaP exposure,and the Hp+BaP combination induced DNA damage in the peripheral lymphocytes of Mongolian gerbils,with the Hp+BaP combination showing synergistic damage.L.salivarius Li01 had a protective effect against DNA damage caused by Hp,BaP,and Hp+BaP.