Objective: To analyze the status and trends of the disease burden of periodontal disease among women of reproductive age (15-49 years) in China from 1990 to 2021, and to provide a reference for the development of periodontal disease prevention and control strategies for women of reproductive age. Methods: Using the global burden of disease (GBD) data from 1990 to 2021, this study investigated the periodontal disease burden among women of reproductive age, including prevalence, incidence, disability-adjusted life years (DALYs), DALY rates, and their corresponding standardized indicators. Joinpoint 5.2.0.0 software was used for time trend analysis of DALYs, age-specific DALY rates, and annual average percentage change (AAPC) values. A log-linear regression model was used to test trends for DALYs and DALY rates. Results: Compared with 1990, the prevalence and incidence of periodontal disease among Chinese women in 2021 increased by 45.67% (per 100,000 people) and 29.29% (per 100,000 people), respectively. The distribution of periodontal disease among women (15-49 years) showed a continuous and rapid upward trend, with the growth rate increasing rapidly with age. The number of cases increased the fastest in the 45-49 age group, and the prevalence increased the fastest in the 35-44 age group. The incidence of periodontal disease continued to rise with age, with the fastest increase in the 35-44 age group among women of reproductive age. The Joinpoint regression model results showed that periodontal disease led to an expanding trend in the disease burden among women of reproductive age in China, with an AAPC of DALYs = 1.20% and an AAPC of DALY rate = 1.25% (P<0.001). Conclusion The periodontal disease burden among Chinese women aged 15-49 years showed a gradually increasing trend from 1990 to 2021.

Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

Prosthesis loosening is the leading cause of postoperative revision in unicompartmental knee arthroplasty (UKA). The deviation of medial and lateral translational installation of the prosthesis during surgery is a common clinical phenomenon and an important factor in increasing the risk of prosthesis loosening. This study established a UKA finite element model and a bone-prosthesis fixation interface micromotion prediction model. The predicted medial contact force and joint motion of the knee joint from a patient-specific lower extremity musculoskeletal multibody dynamics model of UKA were used as boundary conditions. The effects of 9 femoral component medial and lateral translational installation deviations on the Von Mises stress of the proximal tibia, the contact stress, and the micro-motion of the bone prosthesis fixation interface were quantitatively studied. It was found that compared with the neutral position (a/A of 0.492), the lateral translational deviation of the femoral component significantly increased the tibial Von Mises stress and the bone-prosthesis fixation interface contact stress. The maximum Von Mises stress and the maximum contact stress of the fixation interface increased by 14.08% and 143.15%, respectively, when a/A was 0.361. The medial translational deviation of the femoral component significantly increased the bone-prosthesis fixation interface micro-motion. The maximum value of micromotion under the conditions of femoral neutral and medial translation deviation was in the range of 20-50 μm, which is suitable for osseointegration. Therefore, based on considerations such as the micromotion range suitable for osseointegration reported in the literature, the risk of reducing prosthesis loosening, and factors that may induce pain, it is recommended that clinicians control the mounting position of the femoral component during surgery within the safe range of 0-4 mm medial translation deviation.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Finite Element Analysis ; Biomechanical Phenomena ; Knee Prosthesis ; Tibia/surgery* ; Femur/surgery* ; Stress, Mechanical ; Prosthesis Failure ; Knee Joint/surgery* ; Prosthesis Design

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To investigate the clinical value of neuroendoscopic resection in recurrent or residual sellar and clivus tumors and the prevention and treatment of operative complications.Methods:A retrospective study was performed. Clinical data of 49 patients with residual or recurrent sellar and clivus tumors after neuroendoscopic resection in Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University from November 2021 to October 2023 were collected; 45 patients were with pituitary adenoma, 3 were with craniopharyngioma, and 1 patient was with clivus chordoma; their surgical efficacy and complications were summarized and analyzed.Results:Total resection was achieved in 29 patients (59.2%), subtotal resection in 12 (24.5%), and partial resection in 8 (16.3%). Two patients (4.1%) had intraoperative internal carotid artery rupture and were given emergency laminar stenting, discharging with good recovery, but one of them left with unilateral motor nerve palsy. During 1-24 months of follow-up, 97.2% patients (35/36) had headache relief and visual acuity improvement, and no patient had permanent diabetes insipidus or cerebrospinal fluid rhinorrhea. Residual tumors increased in 3 patients (6.1%); no tumor recurrence after total resection was noted.Conclusion:Endoscopic resection of recurrent or residual sellar and clivus tumors is safe and effective; attention should be paid to the internal carotid artery during the operation.

ObjectiveThe mechanisms underlying therapeutic efficacies of Detumescence Analgesic Plaster was analyzed based on "effect-target" associations. MethodBased on CNKI and PubMed databases， the chemical components of Artemisia seed， bastard speedwell， and menthol in Detumescence Analgesic Plaster were collected. The capacity of transdermal absorption was predicted based on the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0）. Golden Triangle of compounds with Accepted used for candidate target prediction based on the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0）according to the similarity of chemical structures. At the same time， the SoFDA data platform was employed to collect the symptoms related to the efficacy of Detumescence Analgesic Plaster and its related genes information. In addition， based on the interaction between the above-mentioned candidate targets and their efficacy-related genes， the "effect-target" interaction network of Detumescence Analgesic Plaster was constructed. The key targets by topological features calculation， and functional mining was carried out to explain the efficacy mechanism of Detumescence Analgesic Plaster. ResultA total of 165 candidate targets were obtained based on ETCM 2.0 and TCMIP v2.0 databases， and symptoms related to the efficacy of clearing heat， detumescence， and relieving pain， as well as 1 744 related genes were collected based on the SoFDA database. Network construction and analysis showed that the core effect targets of Detumescence Analgesic Plaster were mainly involved in regulating the "immune-inflammation" balance of the body and maintaining the homeostasis of material and energy metabolism， blood circulation， and nervous system functions， and they were closely related to the efficacy of this prescription in clearing heat， reducing detumescence， and relieving pain. Among them， the heat clearing group of Detumescence Analgesic Plaster had the functions of heat clearing， detoxifying， antibacteria， and anti-inflammation. The biological function of its key effect target group was related to correcting the imbalance of "immune-inflammation" induced by pathogens. The detumescence group of Detumescence Analgesic Plaster had the functions of reducing water and swelling and resolving hard lumps， and the biological function of its core effect target group was related to improving microcirculation disturbance. The pain relieving group of Detumescence Analgesic Plaster had the functions of removing stasis， promoting blood circulation， and relieving pain， and its core effect target group was related to correcting the nervous system and the disorder of material and energy metabolism. ConclusionThe heat clearing， swelling reducing， and pain relieving effects of Detumescence Analgesic Plaster may be closely related to its act on related candidate targets， so as to correct the imbalance of "nerve-immunity-vascular-axis"， regulate neuronal excitability and inflammatory response， and intervene in material and energy metabolism. The relevant research results lay a theoretical foundation for clarifying the advantages of Detumescence Analgesic Plaster and assisting its clinical precise positioning.

Objective : To investigate the protective effect of melatonin (MT) on formaldehyde (FA) inhalation-in- duced acute lung injury (ALI) in rats and its mechanism through the regulation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway． Methods : Fifty female Wistar rats were randomly divided into Control group ，FA group，FA + MT 5 mg / kg group，FA + MT 10 mg / kg group and FA + MT 20 mg / kg group，with 10 rats in each group．Except for the Control group，all other groups inhaled 3 mg / m3 FA daily for 21 d consecutively to construct the tainted model，and then treated with different MT doses for 14 d．The tainting was continued during the MT treatment．Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue，lung water content and lung coefficient were weighed and measured，glutathione ( GSH) ，superoxide dismutase (SOD) and 8-hydroxydeoxyguanosine ( 8-OHdG) levels were measured by absorbance photometric method ，and enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-α) ，in- terleukin (IL) -6，and IL-1 β concentrations，Western blot to detect the protein expression levels of Nrf2，heme ox- ygenase-1 (HO-1) ，nuclear factor-κB ( NF-κB) ，and phosphorylated nuclear factor-κB ( p-NF-κB) in lung tis- sues，and quantitative polymerase chain reaction(qPCR) to detect the Nrf2，HO-1，and Kelch-like ECH-associated protein 1 (Keap1) mRNA expression levels. Results : Compared with the control group，lung injury was obvious in rats in the FA group ; lung tissue GSH and SOD levels were reduced ，and 8-OHdG levels were elevated ( P < 0. 05) ; alveolar lavage fluid TNF-α , IL-6，and IL-1 β levels were elevated (P＜0. 05) ; Nrf 2 and HO-1 protein expression levels were reduced in the lung tissue (P＜0. 05) ，and p-NF-κB protein expression levels were was ele- vated (P＜0. 05) ; the relative mRNA expression of Nrf2 and HO-1 in lung tissue was decreased，and the relative mRNA expression of Keap1 was elevated (P＜0. 05) ．Compared with the FA group，the lung injury of rats in the MT group was improved ; the levels of GSH and SOD in the lung tissue were increased (P＜0. 05) ，and the level of 8-OHdG was decreased (P＜0. 05) ; the levels of TNF-α , IL-6，and IL-1 β in the alveolar lavage fluid were de- creased (P＜0. 05) ; and the expression levels of the Nrf2 and HO-1 proteins in the lung tissue were increased (P ＜0. 05) ．p-NF-κB protein expression level was decreased (P ＜0. 05) ; the relative mRNA expression levels of Nrf2 and HO-1 in lung tissues were increased (P＜0. 05) ，and the relative mRNA expression level of Keap1 was decreased (P＜0. 05) in lung tissues，and all of them were in a dose-dependent manner． Conclusion MT can al- leviate oxidative stress and inflammatory responses and mitigate FA exposure-induced acute lung injury by regula- ting the Nrf2 / Keap1 / HO-1 signaling pathway.

Abstract: In the present study, the compound XL-12 from our previous work was utilized as a lead compound. Through the optimization of the terminal phenyl ring, 12 target compounds were designed and synthesized. The structures of all target compounds were confirmed by 1H NMR, 13C NMR, and H RMS. In vitro enzyme activity assay showed that most compounds demonstrated significant inhibitory activity toward Bruton’s tyrosine kinase (BTK) and Janus kinase 3 (JAK3). Among them, compound I-3 exhibited moderate cell proliferation inhibitory activity toward Daudi cells and BaF3-JAK3 cells. In the evaluation of anti-inflammatory activity in vitro, compound I-3 could effectively inhibit the production of inflammatory factors IL-6; besides, it exhibited superior anti-inflammatory activity compared to ibrutinib in xylene-induced ear swelling model in mice.

Objective:To investigate the clinical characteristics of first-episode and recurrent acute hypertriglyceridemic pancreatitis (HTGP).Methods:The retrospective cohort study was con-ducted. The clinical data of 313 patients with HTGP admitted to 26 medical centers in China in the Chinese Acute Pancreatitis Clinical Research Group (CAPCTG)-PERFORM database from November 2020 to December 2021 were collected. There were 219 males and 94 females, aged 38(32,44)years. Of the 313 patients, 193 patients with first-episode HTGP were allocated into the first-episode group and 120 patients with recurrent HTGP were allocated into the recurrent group. Observation indica-tors: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) comparison of severity and prognosis in the course of disease within 14 days between the two groups; (3) the association between recurrent HTGP and the risk of persistent organ failure (POF); (4) follow-up. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the Wilcoxon rank sum test. The Kaplan-Meier method was used to plot the cumulative recurrence rate curve and Log-Rank test was used for survival analysis. The Logistic regression model was used for multivariate analysis, and continuous variables were converted into categorical variables according to the mean value or common criteria. Propensity score matching was performed by 1∶1 nearest neighbor matching method, with caliper value of 0.02. Paired t test or Wilcoxon rank sum test and McNemar′s test were used for comparison between matched groups. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 313 patients,208 cases were successfully matched, including 104 cases in the first-episode group and 104 cases in the recurrent group. After propensity score matching, there was no significant difference in demographic characteristics, severity of illness scores and laboratory test between the two groups ( P>0.05). The elimination of gender, acute physiology and chornic health evaluation (APACHE) Ⅱ score, computed tomography severity index score, systemic inflammatory response syndrome score, sequential organ failure assessment score, apolipoprotein E, C-reactive protein, creatinine, lactic acid dehydrogenase, procal-citonin confounding bias ensured comparability between the two groups. (2) Comparison of severity and prognosis in the course of disease within 14 days between the two groups. There were signifi-cant differences in POF and local complications between the first-episode group and the recurrent group ( P<0.05). (3) The association between recurrent HTGP and the risk of POF. Results of uncor-rected univariate analysis showed that there was no association between recurrent HTGP and the risk of POF ( odds ratio=0.78, 95% confidence interval as 0.46-1.30, P>0.05). Results of multivariate analysis after adjusting for covariates such as gender, age, APACHE Ⅱ score, C-reactive protein, triglyceride and total cholesterol showed that compared with first-episode HTGP, recurrent HTGP was associated with a higher risk of POF ( odds ratio=2.22, 95% confidence interval as 1.05-4.71, P<0.05). Results of subgroup analysis showed that age<40 years was associated with an increased risk of POF ( odds ratio=3.31, 95% confidence interval as 1.09-10.08, P<0.05). (4) Follow-up. Twelve of the 313 patients died during hospitalization, including 9 cases in the first-episode group and 3 cases in the recurrent group. The rest of 301 surviving patients, including 184 cases in the first-episode group and 117 cases in the recurrent group, were followed up for 19.2(15.5, 21.9)months. Results of follow-up showed that for 184 survived patients of the first-episode group, 164 cases were followed up and 24 cases experienced recurrence, for 117 survived patients of the recurrent group,29 cases experienced recurrence, showing a significant difference between the two groups ( χ2=4.67, P<0.05). Conclusion:Compared with first-episode HTGP, patients with recurrent HTGP are more prone to POF and local complications, and are more prone to recurrence after discharge. The risk of POF in recurrent HTGP patients is 2.22 times that of those with first-episode, and the risk is higher in patients with age <40 years.