OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke， and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025， wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment， patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data， metabolic phenotype， the levels of platelet function indicators and inflammatory cytokines. Variables with P ＜0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included； among them， 162 cases were normal metabolic phenotype， 218 were intermediate metabolic phenotype， and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment， platelet aggregation rate， the levels of P-selectin and platelet activated complex-1 （PAC-1）， high-sensitivity C-reactive Protein （hs-CRP）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in the normal metabolic phenotype group， intermediate metabolic phenotype group， and poor metabolic phenotype group （except for platelet aggregation rate， and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group） were significantly lower than those before treatment in the same group. Moreover， the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time， and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time （ P ＜0.05）. Univariate and multivariate Logistic regression analyses showed that combined with hypertension， combined with diabetes mellitus， and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke （ P ＜0.05）. Multiple linear regression analysis showed that serum levels of hs-CRP， IL-1β， IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype （ P ＜0.05）， with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype； CYP2C19 gene polymorphism， and in combination with hypertension and diabetes， can be used as independent predictors of poor prognosis.

This study primarily investigates the effect of Liuwei Dihuang Pills on the activation and proliferation of female germline stem cells(FGSCs) in the ovaries and cortex of mice with premature ovarian failure(POF), and how it improves ovarian function. ICR mice were randomly divided into the control group, model group, Liuwei Dihuang Pills group, Liuwei Dihuang Pills double-dose group, and estradiol valerate group. A mouse model of POF was established by intraperitoneal injection of cyclophosphamide. After successful modeling, the mice were treated with Liuwei Dihuang Pills or estradiol valerate for 28 days. Vaginal smears were prepared to observe the estrous cycle and body weight. After the last administration, mice were sacrificed and sampled. Serum levels of estradiol(E_2), follicle-stimulating hormone(FSH), luteinizing hormone(LH), and anti-Müllerian hormone(AMH) were measured by enzyme-linked immunosorbent assay(ELISA). Hematoxylin-eosin(HE) staining was used to observe ovarian morphology and to count follicles at all stages to evaluate ovarian function. Immunohistochemistry was used to detect the expression of mouse vasa homolog(MVH), a marker of ovarian FGSCs. Immunofluorescence staining, using co-labeling of MVH and proliferating cell nuclear antigen(PCNA), was used to detect the expression and localization of specific markers of FGSCs. Western blot was employed to assess the protein expression of MVH, octamer-binding transcription factor 4(Oct4), and PCNA in the ovaries. The results showed that compared with the control group, the model group exhibited disordered estrous cycles, decreased ovarian index, increased atretic follicles, and a reduced number of follicles at all stages. FSH and LH levels were significantly elevated, while AMH and E_2 levels were significantly reduced, indicating the success of the model. After treatment with Liuwei Dihuang Pills or estradiol valerate, hormone levels improved, the number of atretic follicles decreased, and the number of follicles at all stages increased. MVH marker protein and PCNA proliferative protein expression in ovarian tissue also increased. These results suggest that Liuwei Dihuang Pills regulate estrous cycles and hormone disorders in POF mice, promote the proliferation of FGSCs, improve follicular development in POF mice, and enhance ovarian function.
Animals ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Cell Proliferation/drug effects* ; Mice, Inbred ICR ; Ovary/cytology* ; Primary Ovarian Insufficiency/genetics* ; Follicle Stimulating Hormone/metabolism* ; Humans ; Anti-Mullerian Hormone/blood* ; Antineoplastic Agents/adverse effects* ; Luteinizing Hormone/metabolism* ; Cyclophosphamide/adverse effects*

Alveolar bone reconstruction simulation is an effective means for quantifying orthodontics, but currently, it is not possible to directly obtain human alveolar bone material models for simulation. This study introduces a prediction method for the equivalent shear modulus of three-dimensional random porous materials, integrating the first-order Ogden hyperelastic model to construct a computed tomography (CT) based porous hyperelastic Ogden model (CT-PHO) for human alveolar bone. Model parameters are derived by combining results from micro-CT, nanoindentation experiments, and uniaxial compression tests. Compared to previous predictive models, the CT-PHO model shows a lower root mean square error (RMSE) under all bone density conditions. Simulation results using the CT-PHO model parameters in uniaxial compression experiments demonstrate more accurate prediction of the mechanical behavior of alveolar bone under compression. Further prediction and validation with different individual human alveolar bone samples yield accurate results, confirming the generality of the CT-PHO model. The study suggests that the CT-PHO model proposed in this paper can estimate the material properties of human alveolar bone and may eventually be used for bone reconstruction simulations to guide clinical treatment.
Humans ; Tomography, X-Ray Computed/methods* ; Porosity ; Alveolar Process/physiology* ; Bone Density ; Computer Simulation ; Elasticity ; X-Ray Microtomography ; Stress, Mechanical ; Finite Element Analysis ; Models, Biological

OBJECTIVE: To explore the expression and clinical significance of programmed death receptor 1 (PD-1), Th1, Th2, and Th17 cytokines in multiple myeloma (MM). METHODS: A total of 76 MM patients treated in the Tengzhou Central People's Hospital from May 2021 to May 2023 were collected as MM group, and 48 healthy individuals who underwent physical examination during the same period were included as control group. The expression of PD-1 on the surface of CD4⁺ and CD8⁺ T cells and the levels of serum Th1 cytokines ［interleukin (IL) -2, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α)］, Th2 cytokines (IL-4, IL-6, IL-10) and Th17 cytokines (IL-17) were detected in the two groups. Spearman correlation was used to examine the relationship between PD-1, Th1, Th2 and Th17 cytokines and clinical stage and immune typing of MM patients. Multivariate logistic regression analysis was used to analyze the related factors affecting the efficacy of chemotherapy in MM patients, and the factors were tested for multicollinearity. Receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of PD-1, Th1, Th2 and Th17 cytokines in chemotherapy efficacy of MM patients. RESULTS: The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in the MM group were higher than those in the control group, while the levels of IL-2, IFN-γ, and TNF-α were lower (all P <0.001). The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in R-ISS stage III patients were higher than those in stage II and I patients, and the levels in stage II patients were higher than those in stage I patients (all P <0.05). The IL-2 level in R-ISS stage III patients was lower than that in stage II and I patients, and IL-2 level in R-ISS stage II patients was lower than that in stage I patients (all P <0.05). The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in IgG patients were higher than those in IgA, light chain, and non secretory patients, while the level of IL-2 was lower (all P <0.05). Correlation analysis showed that CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 were positively correlated with R-ISS staging in MM patients (r =0.623, 0.635, 0.728, 0.330, 0.742, 0.412), and negatively correlated with immune classification (r =-0.664, -0.756, -0.642, -0.479, -0.613, -0.323). IL-2 was negatively correlated with R-ISS staging in MM patients (r =-0.280), and positively correlated with immune classification (r =0.483). The levels of CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10, and IL-17 in the non-remission group were higher than those in the remission group, while the level of IL-2 was lower (all P <0.001). Multivariate logistic regression analysis showed that the increased CD4⁺T PD-1, CD8⁺T PD-1, IL-4, IL-6, IL-10 and IL-17 were risk factors for the efficacy of chemotherapy in MM patients (OR >1, P <0.05), while the increased IL-2 was a protective factor (OR < 1, P <0.05). The results of multicollinearity test showed that the tolerance of the seven factors included was between 0.714-0.885, and the variance inflation factor was between 1.130-1.400. There was no multicollinearity. The ROC curve analysis results showed that the area under the curve for the combined prediction of chemotherapy efficacy in MM patients by the above 7 factors was 0.942, with specificity of 0.741 and sensitivity of 0.909. CONCLUSION The expression levels of PD-1 on the surface of CD4⁺ and CD8⁺ T cells and serum Th2 and Th17 cytokines in MM patients are high, while Th1 cytokines are low. PD-1, Th1, Th2, and Th17 cytokines are related to clinical stage and immune classification of MM patients. The combined detection of these indicators can help predict the chemotherapy efficacy of MM patients.
Humans ; Programmed Cell Death 1 Receptor/metabolism* ; Multiple Myeloma/blood* ; Cytokines/metabolism* ; Th17 Cells/metabolism* ; Th1 Cells/metabolism* ; Th2 Cells/metabolism* ; Female ; Male ; Interleukin-10 ; Interferon-gamma ; Middle Aged ; Interleukin-17 ; Interleukin-2 ; Interleukin-4 ; Tumor Necrosis Factor-alpha ; Interleukin-6 ; Aged

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To retrospectively analyze the clinical risk factors and prognosis of perioperative myocardial injury(MINS)in non-cardiac surgery patients admitted to the intensive care unit(ICU).Methods A total of 478 postoperative patients admitted to the Department of Intensive Medicine,Minhang Hospital,Fudan University from Jan 2020 to Dec 2023 were selected.They were divided into MINS group(n=302)and normal group(n=176)based on whether myocardial injury occurred within 7 days after surgery.The differences in clinical characteristics between the two groups were compared,and risk factors for perioperative myocardial injury were identified.Risk factors for mortality in the MINS group were analyzed with 30-day mortality as the clinical endpoint.Results The prevalence of acute physiology and chronic health evaluation Ⅱ(Apache Ⅱ)score,coronary artery disease,and chronic kidney disease were all higher in the MINS group than those in the normal group,with statistically significant differences(P<0.05).The proportion of emergency surgeries,co-infection,and perioperative hypotension were significantly different between the MINS group and the normal group(P<0.05).Multivariate logistic regression analysis revealed that chronic kidney disease,emergency surgery,co-infection,and intraoperative and postoperative hypotension were risk factors for MINS occurrence.Prognostic analysis indicated that perioperative hypotension was a risk factor for 30-day mortality in MINS patients.Conclusion MINS is closely associated with patients'underlying conditions,timing of surgery,and perioperative hypotension status,and especially perioperative hypotension affects the final outcomes.

Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Objective To compare the differences of baseline characteristics of patients with myelodysplastic syndrome(MDS)who achieved platelet(PLT)response after arsenic-containing TCM compounds combined with Western medicine treatment.Methods Totally 72 MDS patients were selected from 12 outpatient departments and wards,such as Xiyuan Hospital,China Academy of Chinese Medical Sciences,Dongfang Hospital,Beijing University of Chinese Medicine from October 2021 to October 2024.Among them,45 patients received arsenic-containing TCM compounds combined with Western medicine treatment,27 patients received Western medicine treatment.The blood routine[white blood cell(WBC)count,hemoglobin,PLT,neutrophil count],TCM syndrome scores,safety indicators,and adverse events were observed before and after three courses of treatment.The efficacy of all patients was evaluated,and the baseline characteristics of patients who achieved PLT response in the arsenic-containing TCM compounds group and the Western medicine treatment group were compared.Results Comparing the differences of baseline characteristics of the two groups,it was found that the patients who achieved PLT response in the arsenic-containing TCM compounds group were compared with those in the Western medicine treatment group:Age<60 years old(P=0.038),longer disease duration(P=0.012),lower WBC(P=0.017),lower reticulocyte percentage(P=0.037),lower blood urea nitrogen(P=0.046),lower high-density lipoprotein cholesterol(P=0.014),and lower N-terminal pro-B-type natriuretic peptide(P=0.034),abnormal electrocardiogram(P=0.013),high blasts(P=0.009),grade 0 reticular fiber staining(P<0.01),normal chromosome karyotype(P<0.01),gene mutation(P<0.01)and high TCM syndrome scores(P=0.013)were found.Conclusion Arsenic-containing TCM compounds consisting of Qinghuang Powder and Bushen Jianpi Decoction combined with Western medicine is used to treat MDS.Patients with age<60 years old,long disease duration,low WBC count,low reticulocyte percentage,low blood urea nitrogen,low high-density lipoprotein cholesterol,low N-terminal pro-B-type natriuretic peptide,abnormal electrocardiogram,high blasts,grade 0 reticular fiber staining,normal chromosome karyotype,gene mutation and high TCM syndrome score are more likely to obtain PLT response.

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.