OBJECTIVE: To assess the efficacy and safety of a new conditioning regimen with chidamide and BEAM for autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma. METHODS: Medical records and further follow-up data from 85 patients with lymphoma from May 2015 to September 2020 in our hospital were retrospectively collected and analyzed. RESULTS: Among 85 patients, 52 cases accepted BEAM regimen and 33 cases accepted CBEAM followed by AHSCT. In CBEAM group, 18 patients (54.5%) received AHSCT as salvage therapy, while only 26.9% (14 cases) for salvage in BEAM group ( P < 0.01). CBEAM conditioning resulted in shorter neutrophil engraftment of 2 days, while no significant difference was found in platelet engraftment. Although the incidence of liver impairment was higher in CBEAM group (12.1%), the grade of impairment was only Ⅰ to Ⅱ. The two conditioning regimens both achieved good complete remission rate of over 90%, and no transplant-related death occurred. The median follow-up time in the CBEAM group was 18(12, 22) months, and 39(20, 59) months in the BEAM group. There were no significantly differences in 2-year progression-free survival (PFS) and overall survival (OS) rate between the two groups (P >0.05). In patients with refractory or relapsed non-Hodgkin lymphoma, the 2-year PFS rate after transplantation in BEAM group and CBEAM group was 74.1% and 92.9%, respectively (P >0.05), indicating that chidamide may have certain advantages in prolonging PFS. CONCLUSION CBEAM conditioning regimen has a good efficacy and safety in lymphoma patients before AHSCT, especially in refractory and relapsed non-Hodgkin lymphoma patients, suggesting that it could serve as an alternative conditioning regimen prior to AHSCT for lymphoma.
Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning/methods* ; Transplantation, Autologous ; Retrospective Studies ; Aminopyridines/therapeutic use* ; Lymphoma/therapy* ; Benzamides/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Male ; Female ; Cytarabine/therapeutic use* ; Melphalan/therapeutic use* ; Adult ; Middle Aged ; Podophyllotoxin/therapeutic use* ; Carmustine ; Etoposide

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

OBJECTIVES: To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). METHODS: This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. RESULTS: The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). CONCLUSIONS GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve.
Adult ; Female ; Humans ; Genotype ; Ovarian Follicle/cytology* ; Ovarian Reserve/genetics* ; Ovulation Induction/methods* ; Polymorphism, Genetic ; Receptors, Androgen/genetics* ; East Asian People/genetics*

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the value of optical coherence tomography(OCT)in predicting the risk of major adverse cardiovascular events(MACE)in patients of acute coronary syndrome(ACS).Methods Four hundred and forth-eight ACS patients admitted to the First Affiliated Hospital of Xinjiang Medical University who underwent percutaneous coronary intervention(PCI)and OCT from February 2015 to February 2022 were selected as the study subjects.We found 749 non-culprit coronary lesions.And follow up the patients,median follow-up was 5 years[interquartile interval(IQR):3-7 years].Kaplan-meier was used to estimate the cumulative incidence of MACE,multivariate Cox regression was used to analyze the risk of MACE with OCT parameters non-culprit coronary lesions,and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of OCT parameters for MACE in non-culprit coronary lesions.Results A total of 749 non-culprit coronary lesions were detected,and 41 MACE cases were caused by non-culprit coronary lesions imaged by OCT.Compared with plaques without thin-cap fibroatheroma(TCFA)and minimal lumen area(MLA)＜3.5 mm2,the incidence of MACE was significantly associated with vulnerable plaques with TCFA and MLA＜3.5 mm2(33％vs.3％,HR 13.62,95％CI 6.71-27.65,P＜0.001).Multivariate Cox regression analysis showed that larger maximum lipid arc(HR 1.02,95％CI 1.01-1.03,P＜0.001),smaller maximum lipid cap thickness(HR 0.97,95％CI 0.96-0.99,P＜0.001)and MLA(HR 0.31,95％CI 0.18-0.55,P＜0.001)were independent risk factors for MACE.The area under ROC curve(AUC)of the thinnest fiber cap thickness for predicting MACE occurrence was 0.858(95％CI 0.802-0.913),and the optimal cutoff value was 66.5 μm.The AUC of maximum lipid arc for predicting MACE occurrence was 0.853(95％CI 0.786-0.920),and the optimal cut-off value was 180.35°.The AUC of MLA for predicting MACE was 0.821(95％CI 0.766-0.876),and the optimal cutoff was 3.575 mm2.Conclusions The non-culprit coronary lesions with TCFA and MLA＜3.5 mm2 were significantly associated with an increased risk of subsequent MACE development at the lesion level,and OCT imaging helps early identification of the risk of MACE development in non-culprit coronary lesions in patients of ACS.

Objective:To investigate the prognostic value of tumor mutation burden(TMB)in pancreatic neuroendocrine tumours(PanNETs).Methods:Data of 96 PanNETs patients was in-cluded in the study and cut-off value of TMB was determined according to the time dependent re-ceiver operator characteristic(ROC)curve and area under the curve(AUC).Logistic regression analysis was used to determine the clinical and pathological features associated with TMB.Cox re-gression analysis was used to detect the correlation between TMB and the overall survival time(OS)of patients.Kaplan-Meier method was used to construct the survival curve.Results:Ac-cording to the time dependent ROC curve and AUC,the optimal truncation value of TMB was deter-mined to be 0.6 mut/Mb.Logistic regression analysis indicated that high TMB was independently correlated with age[OR=1.126(1.057-11.199),P＜0.001]and extrapancreatic spread[OR=15.931(2.228-113.892),P=0.006].Kaplan-Meier curve showed that patients with high TMB had a poor OS[HR=5.042(1.41917.917),P=0.012].Multivariate Cox regression analysis indicated that TMB was an independent prognostic factor of PanNETs[HR=7.578(1.409-40.744),P=0.018].Conclusion:TMB is independently correlated with age and extrapancreatic spread,and is an independent prog-nostic factor for PanNETs patients and PanNETs patients with high TMB have a poorer prognosis.

T cell infiltration and proliferation in tumor tissues are the main factors that significantly affect the therapeutic outcomes of cancer immunotherapy. Emerging evidence has shown that interferon-gamma (IFNγ) could enhance CXCL9 secretion from macrophages to recruit T cells, but Siglec15 expressed on TAMs can attenuate T cell proliferation. Therefore, targeted regulation of macrophage function could be a promising strategy to enhance cancer immunotherapy via concurrently promoting the infiltration and proliferation of T cells in tumor tissues. We herein developed reduction-responsive nanoparticles (NPs) made with poly (disulfide amide) (PDSA) and lipid-poly (ethylene glycol) (lipid-PEG) for systemic delivery of Siglec15 siRNA (siSiglec15) and IFNγ for enhanced cancer immunotherapy. After intravenous administration, these cargo-loaded could highly accumulate in the tumor tissues and be efficiently internalized by tumor-associated macrophages (TAMs). With the highly concentrated glutathione (GSH) in the cytoplasm to destroy the nanostructure, the loaded IFNγ and siSiglec15 could be rapidly released, which could respectively repolarize macrophage phenotype to enhance CXCL9 secretion for T cell infiltration and silence Siglec15 expression to promote T cell proliferation, leading to significant inhibition of hepatocellular carcinoma (HCC) growth when combining with the immune checkpoint inhibitor. The strategy developed herein could be used as an effective tool to enhance cancer immunotherapy.

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.