Objective: To investigate the inhibitory effect of neoeriocitrin (Neo) on ligature-induced experimental periodontitis in mice and evaluate its biosafety, providing experimental evidence for novel candidate drugs in periodontitis treatment. Methods: This study has been approved by the Animal Welfare and Ethical Safety Committee. A periodontitis model was established in C57BL/6J mice using silk ligation. The mice were divided into control, periodontitis model, and three Neo treatment groups (5, 10, 20 mg/kg Neo). After 2 weeks of intervention, alveolar bone resorption was analyzed by micro-computed tomography (micro-CT); periodontal tissue pathological changes were observed via hematoxylin-eosin (HE) and Masson staining; osteoclasts were counted using tartrate-resistant acid phosphatase staining; serum inflammatory factor levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-10 (IL-10)] were detected by enzyme-linked immunosorbent assay; gut microbiota changes were analyzed by 16S rRNA sequencing; and biosafety was assessed through HE staining of the heart, liver, spleen, lung, kidney, and colon, as well as zonula occludens-1 (ZO-1) immunohistochemical staining of the colon. Results: Compared with the periodontitis model group, the 10 mg/kg Neo treatment group showed significantly alleviated alveolar bone resorption, manifested as reduced cementoenamel junction to alveolar bone crest distance, increased bone mineral density, bone volume fraction, and trabecular thickness. Additionally, reduced inflammatory cell infiltration, improved collagen fiber arrangement, and a significantly decreased number of osteoclasts were observed in periodontal tissues. Serum levels of pro-inflammatory factors TNF-α and IL-6 were also reduced. Furthermore, 10 mg/kg Neo intervention modulated the gut microbiota structure without causing significant multi-organ toxicity or impairing intestinal barrier function. Conclusion Neo can effectively mitigate the progression of experimental periodontitis by inhibiting alveolar bone resorption, reducing periodontal tissue inflammation, modulating systemic immunity, and improving gut microbiota. With good biosafety, Neo is a promising candidate drug for the treatment of periodontitis.

ObjectiveTo analyze the distribution, drug resistance characteristics, and changing trends of Acinetobacter baumannii (AB) isolated from environmental surfaces and healthcare workers’ hands in a grade Ⅱ level A general hospital in Xuhui District of Shanghai from 2018 to 2023, and to provide reference for infection control in the hospital. MethodsEnvironmental samples were collected quarterly from critical surfaces and healthcare workers’ hands in the intensive care unit (ICU), geriatrics, and respiratory departments from 2018 to 2023. Clinical isolates were obtained from all patients with AB infections in ICU, geriatrics, respiratory department, rehabilitation department, infectious diseases department, emergency department, cardiology department, and orthopedics of the hospital from 2018 to 2023. Retrospective analyses were performed on AB detection rates, strain origins, resistance rates to commonly used antimicrobial agents, and resistance gene features, comparing the antimicrobial resistance between clinically isolated strains and environmentally isolated strains. ResultsFrom 2018 to 2023, a total of 1 416 samples were collected from the hospital and a total of 272 strains of AB were detected, with a positive detection rate of 19.21%. The detection rate gradually decreased year-on-year (χ²_trend=45.290, P<0.001). The majority of samples originated from patient-contacted items (34.56%, 94/272), followed by shared items (26.84%, 73/272) and healthcare worker-contacted items (15.07%, 41/272). From 2018 to 2023, the resistance rate of AB on environmental surfaces and healthcare workers’ hands to commonly tested antibiotics in the hospital ranged from 10% to 40%. The resistance rates to cefotaxime (42.52%) and piperacillin (38.58%) were relative high, while the resistance to polymyxin E (1.57%), polymyxin B (2.36%), and doxycycline (3.94%) maintained low. The annual fluctuations in resistance to cefotaxime, piperacillin, ceftriaxone, tobramycin, doxycycline, minocycline and cotrimoxazole were statistically significant (all P<0.05). There were statistically significant differences in the resistance of clinical and environmental isolates to ampicillin/sulbactam, cefepime, ceftazidime, subamphetamine, meropenem, piperacillin, aztreonam, gentamicin, tobramycin, minocycline, ciprofloxacin, levofloxacin, and cotrimoxazole in the hospital from 2018 to 2023 (all P<0.05). The resistance rate of clinical isolates was generally high, especially to β-lactam and quinolone drugs, which were mostly above 80% [such as cefepime (93.86%), cefotaxime (97.37%), imipenem (98.25%), and ciprofloxacin (99.12%)]. The resistance rate of environmental isolated strains to similar antibiotics was relatively lower, mostly concentrated at 10%‒30%. The whole-genome sequencing of 34 carbapenem-resistant Acinetobacter baumannii (CRAB) strains isolated from the hospital environment in 2023 revealed that the main resistance mechanism was overexpression of efflux pumps (51.97%), followed by changes in target sites (32.46%). Among the 34 CRAB strains, carbapenem resistance genes OXA-23 and OXA-51 were detected in 6 strains (17.65%), while genes such as KPC, IMP, VIM, and SIM were not detected. ConclusionFrom 2018 to 2023, AB in the hospital environment exhibited high resistance rates to certain antimicrobial agents and carried multiple resistance genes, indicating a potential transmission risk. It is necessary to further strengthen bacterial resistance monitoring and hospital infection control, and use antibiotics reasonably.

Objective To identify key acoustic features associated with the progression of Alzheimer's disease(AD)through voice analysis combined with machine learning and feature selection techniques,thereby constructing classification models that serve as candidate tools for the early screening of AD.Methods Voice samples from AD,mild cognitive impairment(MCI)and healthy(HC)elderly individuals were obtained from the NCMMSC2021 AD voice dataset.The voice samples underwent data preprocessing,followed by feature extraction from the eGeMAPS feature set via the OpenSmile toolkit.Classification models were obtained utilizing random forest and support vector machine(SVM)algorithms.Significance testing and feature importance ranking were conducted using Python,and the further selection of the optimal features was performed through sequential forward selection(SFS).The classification performance before and after feature selection was compared and evaluated using accuracy and the area under the receiver operating characteristic curve(AUC).Results The significant acoustic features in the classification models primarily derived from spectral slope,formant,fundamental frequency,and loudness.The optimal classification performance was achieved with the SVM model following SFS feature selection,with recognition accuracies of 0.926(AUC=0.974)for AD/MCI group,0.875(AUC=0.956)for AD/HC group,and 0.879(AUC=0.904)for MCI/HC group.Conclusion SVM model performs better than random forest model,and the use of SFS for feature selection can effectively enhance model performance.Voice analysis has the potential to serve as a valuable supplementary tool for the rapid AD assessment and screening.

To summarize Professor WANG Xixing's clinical experience in treating advanced breast cancer with anxiety and depression from the perspective of shaoyang pivot. It is believed that the core pathogenesis of advanced breast cancer with anxiety and depression lies in the dysfunction of shaoyang pivot （referring to the imbalanced regulatory function of the shaoyang meridian system that governs the transportation and transformation of qi， blood， and body fluids）. This dysfunction can lead to abnormal circulation of qi， blood， and body fluids， as well as the intermingling of phlegm and blood stasis， which further promotes the spread and diffusion of cancer toxin. Meanwhile， it disturbs mental activity， resulting in a condition characterized by stagnation of cancer toxin and concurrent disorders of both the physical body and the spirit. Based on this pathogenesis， the basic therapeutic principles of harmonizing shaoyang， regulating the pivot to calm the spirit， and dissipating masses and resolving toxins are proposed. Clinically， the disease is classified into three syndromes for differentiation and treatment. For shaoyang pivot dysfunction syndrome， treatment should use self-prescribed Chaiqin Hengshu Ningxin Decoction （柴芩衡枢宁神汤）； for sanjiao pivot dysfunction syndrome， treatment should prescribe Chaigui Tongshu Dashen Decoction （柴归通枢达神饮）； for gallbladder function disorder syndrome， treatment should apply Wendan Qishu Shoushen Decoction （温胆启枢守神汤）. Throughout the treatment process， the concept of "simultaneous treatment of cancer and depression" is implemented to smooth the shaoyang pivot， block the vicious cycle where cancer toxin and emotional abnormalities mutually reinforce each other.

Objective:To investigate the relationship between the morphology of bone marrow plasma cells, the identification of M protein, and the detection of minimal residual disease(MRD)by flow cytometry in elderly patients with multiple myeloma(MM).Additionally, the impact on progression-free survival(PFS)is analyzed.Methods:A total of 60 elderly MM patients with bone marrow morphology reports and corresponding flow MRD detection, collected from February 1, 2017, to January 31, 2022, at Beijing Chaoyang Hospital Affiliated to Capital Medical University, were included in this study.We collected data on plasma cells from morphological examination and flow cytometry-based MRD detection. By combining these findings with M-protein identification results from 35 cases, we analyzed the correlations among these three parameters. Patients were stratified into two groups based on median values of: flow cytometry MRD(0.246% of nucleated cells), morphological plasma cell percentage(3.5%), and M-protein quantification(2.5 g/dl).This stratification enabled evaluation of their prognostic value for PFS.Results:A total of 60 elderly MM patients were enrolled, including 41 males with age of 65.0(63.0, 68.5)years and 19 females with age of 67.0(64.0, 72.0)years The morphology of bone marrow in 60 elderly patients with MM revealed 10 cases of primitive plasma cells(16.67%), 48 cases of immature plasma cells(80.00%), and 2 cases with no plasma cells(3.33%).A positive correlation was observed between the proportion of bone marrow plasma cells and the corresponding flow MRD in terms of both the proportion of nuclear cells and the proportion of plasma cells.Specifically, the proportion of the morphological protoplasma group showed a strong correlation with flow MRD(proportion of plasma cells)( r=0.82, P<0.01), while the proportion of the morphological immature plasma group exhibited moderate correlations with flow MRD(proportion of nuclear cells)( r=0.74, P<0.05)and flow MRD(proportion of plasma cells)( r=0.70, P<0.01).No significant correlation was found between the type and quantity of M protein and flow MRD( P>0.05).The PFS time for the flow MRD ≥0.246%(nucleated cells)group was shorter than that of the<0.246% group( P<0.05).There was no significant difference in PFS between the groups with plasma cell ratios ≥3.5% and<3.5%( P=0.15).Additionally, no significant difference in PFS was observed between patients with M protein quantitation ≥2.5 g/dl and those with M protein quantitation<2.5 g/dl( P=0.94). Conclusions:The proportion of bone marrow plasma cells correlates with flow MRD in elderly patients with MM, and a high MRD load indicates a poor prognosis.However, no significant correlation was found between M protein levels and flow MRD or PFS.Clinical attention should focus on the dynamic monitoring of plasma cell morphology and flow MRD.Nevertheless, the morphological detection of plasma cells remains crucial for auxiliary diagnosis due to its intuitiveness, cost-effectiveness, and broad applicability.

Objective To identify key acoustic features associated with the progression of Alzheimer's disease(AD)through voice analysis combined with machine learning and feature selection techniques,thereby constructing classification models that serve as candidate tools for the early screening of AD.Methods Voice samples from AD,mild cognitive impairment(MCI)and healthy(HC)elderly individuals were obtained from the NCMMSC2021 AD voice dataset.The voice samples underwent data preprocessing,followed by feature extraction from the eGeMAPS feature set via the OpenSmile toolkit.Classification models were obtained utilizing random forest and support vector machine(SVM)algorithms.Significance testing and feature importance ranking were conducted using Python,and the further selection of the optimal features was performed through sequential forward selection(SFS).The classification performance before and after feature selection was compared and evaluated using accuracy and the area under the receiver operating characteristic curve(AUC).Results The significant acoustic features in the classification models primarily derived from spectral slope,formant,fundamental frequency,and loudness.The optimal classification performance was achieved with the SVM model following SFS feature selection,with recognition accuracies of 0.926(AUC=0.974)for AD/MCI group,0.875(AUC=0.956)for AD/HC group,and 0.879(AUC=0.904)for MCI/HC group.Conclusion SVM model performs better than random forest model,and the use of SFS for feature selection can effectively enhance model performance.Voice analysis has the potential to serve as a valuable supplementary tool for the rapid AD assessment and screening.

Objective:To investigate the relationship between the morphology of bone marrow plasma cells, the identification of M protein, and the detection of minimal residual disease(MRD)by flow cytometry in elderly patients with multiple myeloma(MM).Additionally, the impact on progression-free survival(PFS)is analyzed.Methods:A total of 60 elderly MM patients with bone marrow morphology reports and corresponding flow MRD detection, collected from February 1, 2017, to January 31, 2022, at Beijing Chaoyang Hospital Affiliated to Capital Medical University, were included in this study.We collected data on plasma cells from morphological examination and flow cytometry-based MRD detection. By combining these findings with M-protein identification results from 35 cases, we analyzed the correlations among these three parameters. Patients were stratified into two groups based on median values of: flow cytometry MRD(0.246% of nucleated cells), morphological plasma cell percentage(3.5%), and M-protein quantification(2.5 g/dl).This stratification enabled evaluation of their prognostic value for PFS.Results:A total of 60 elderly MM patients were enrolled, including 41 males with age of 65.0(63.0, 68.5)years and 19 females with age of 67.0(64.0, 72.0)years The morphology of bone marrow in 60 elderly patients with MM revealed 10 cases of primitive plasma cells(16.67%), 48 cases of immature plasma cells(80.00%), and 2 cases with no plasma cells(3.33%).A positive correlation was observed between the proportion of bone marrow plasma cells and the corresponding flow MRD in terms of both the proportion of nuclear cells and the proportion of plasma cells.Specifically, the proportion of the morphological protoplasma group showed a strong correlation with flow MRD(proportion of plasma cells)( r=0.82, P<0.01), while the proportion of the morphological immature plasma group exhibited moderate correlations with flow MRD(proportion of nuclear cells)( r=0.74, P<0.05)and flow MRD(proportion of plasma cells)( r=0.70, P<0.01).No significant correlation was found between the type and quantity of M protein and flow MRD( P>0.05).The PFS time for the flow MRD ≥0.246%(nucleated cells)group was shorter than that of the<0.246% group( P<0.05).There was no significant difference in PFS between the groups with plasma cell ratios ≥3.5% and<3.5%( P=0.15).Additionally, no significant difference in PFS was observed between patients with M protein quantitation ≥2.5 g/dl and those with M protein quantitation<2.5 g/dl( P=0.94). Conclusions:The proportion of bone marrow plasma cells correlates with flow MRD in elderly patients with MM, and a high MRD load indicates a poor prognosis.However, no significant correlation was found between M protein levels and flow MRD or PFS.Clinical attention should focus on the dynamic monitoring of plasma cell morphology and flow MRD.Nevertheless, the morphological detection of plasma cells remains crucial for auxiliary diagnosis due to its intuitiveness, cost-effectiveness, and broad applicability.

Periodontitis is a chronic inflammatory and immune reactive disease induced by the subgingival biofilm.The therapeutic effect for susceptible patients is often unsatisfactory due to excessive inflammatory response and oxidative stress.Sinensetin(Sin)is a nature polymethoxylated flavonoid with anti-inflammatory and antioxidant activities.Our study aimed to explore the beneficial effect of Sin on periodontitis and the specific molecular mechanisms.We found that Sin attenuated oxidative stress and inflammatory levels of periodontal ligament cells(PDLCs)under inflammatory conditions.Administered Sin to rats with ligation-induced periodontitis models exhibited a protective effect against periodontitis in vivo.By molecular docking,we identified Bach1 as a strong binding target of Sin,and this binding was further verified by cellular thermal displacement assay and immunofluorescence assays.Chromatin immunoprecipitation-quantitative polymerase chain reaction results also revealed that Sin obstructed the binding of Bach1 to the HMOX1 promoter,subsequently upregulating the expression of the key antioxidant factor HO-1.Further functional experiments with Bach1 knocked down and overexpressed verified Bach1 as a key target for Sin to exert its antioxidant effects.Additionally,we demonstrated that Sin prompted the reduction of Bach1 by potentiating the ubiquitination degradation of Bach1,thereby inducing HO-1 expression and inhibiting oxidative stress.Overall,Sin could be a promising drug candidate for the treatment of periodontitis by targeting binding to Bach1.

Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Gastric cancer is one of the major diseases threatening human health, with a high incidence and a low early diagnostic rate. There are many bottlenecks encountered during its treatment. Consequently, improving the early diagnostic rate and exploring new therapeutic targets are currently urgent challenges that need to be addressed. Telomerase is undetectable in normal tissues, but it exhibits high specificity and sensitivity in most cancers and has a definite correlation with prognosis. It may serve as a serum tumor marker and prognostic indicator. Human telomerase reverse transcriptase (hTERT) gene polymorphism can regulate the susceptibility of people to gastric cancer, and affect the occurrence, development, proliferation and apoptosis of gastric cancer through its target gene. Substances such as resistin, visfatin, G-quadruplex and methylenedioxyaniline can affect the occurrence and development of gastric cancer by regulating telomerase expression. The mechanism by which hTERT regulates tumor invasion and metastasis is currently unclear, so elucidating its mechanism is of great significance.This paper will review the research progress of this mechanism in recent years.