In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

Sulforaphane is a naturally occurring active substance derived from cruciferous vegetables with potent antioxidant and anticancer properties. Researches have shown that sulforaphane has good bioavailability and can be absorbed by the small intestine through passive transport, followed by excretion in the form of urine via the hydrophobic acid pathway. In addition, since sulforaphane is easy to be absorbed and metabolized, wrapping sulforaphane with nanomaterials can improve its bioavailability and stability, prolong its action time in human body, and better utilize its therapeutic effect. In terms of mechanism of action, sulforaphane can activate Nrf2 and HSF1 signaling pathways, induce the expression of phase II detoxification enzymes HO-1, NADPH, GST and HSP, thus regulating the concentration of oxidative stress ROS in vivo; inhibit NF-κB signaling pathway, thus suppressing the expression of inflammatory factors TNF-α, IL-1 and IL-6; regulate epigenetic modifications, thus inhibiting HDAC and DNMT, and increasing the concentration of histone H3 and H4. By regulating the expression levels of the above factors, sulforaphane can affect the occurrence and development of cancer, neurodegenerative diseases and other diseases. In recent years, several phase I/II clinical trials have shown that sulforaphane has good drug-generating properties. For example, researchers have found that patients with skin cancer have not shown any health problems and their corresponding functional problems have improved greatly after long-term use of sulforaphane. This suggests that in the future sulforaphane has a very high medicinal potential for the treatment of cancer and neurodegenerative diseases. In this paper, we review the pharmacokinetics, target of action and safety of sulforaphane and its research progress in tumor and neurodegenerative diseases to provide a reference for the future application of sulforaphane in the treatment of tumor and neurodegenerative diseases.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To evaluate extrathyroidal extension (ETE) in papillary thyroid microcarcinoma (PTMC) with three-dimensional tomographic ultrasound imaging (3D-TUI). Methods A total of 97 thyroid nodules of 79 patients with PTMC treated in PUMC Hospital from February 2016 to January 2018 were included in this study.Two ultrasound experts performed independent blinded assessment of the relationship between thyroid nodules and thyroid capsule by two-dimensional ultrasound (2D-US) and 3D-TUI.The results of 2D-US and 3D-TUI in evaluating ETE were compared with intraoperative findings and postoperative histological and pathological results. Results Among the 97 nodules,54 (55.7%) nodules had ETE.The diagnostic sensitivity (68.5% vs.37.0%;χ²=10.737,P=0.002),accuracy (74.5% vs.56.7%;χ²=6.686,P=0.015),and area under the receiver operating characteristic curve[0.761 (95%CI=0.677-0.845) vs.0.592 (95%CI=0.504-0.680);Z=3.500,P<0.001] of 3D-TUI were higher than those of 2D-US.However,3D-TUI and 2D-US showed no significant difference in the specificity (84.1% vs.81.4%;χ²=0.081,P=0.776),negative predictive value (67.9% vs.50.7%;χ²=3.645,P=0.066),or positive predictive value (84.1% vs.71.4%;χ²=1.663,P=0.240). Conclusion Compared with 2D-US,3D-TUI demonstrates increased diagnostic efficiency for ETE of PTMC.
Humans ; Thyroid Nodule ; Thyroid Neoplasms/diagnosis* ; Carcinoma, Papillary/pathology* ; Ultrasonography/methods* ; Retrospective Studies

OBJECTIVE: To evaluate the characteristics of severe periodontitis with various number of tooth loss during 4-year natural progression, and to analyze the factors related to higher rate of tooth loss. METHODS: A total of 217 patients aged 15 to 44 years with severe periodontitis were included, who participated in a 4-year natural progression research. Data obtained from questionnaire survey, clinical examination and radiographic measurement. Tooth loss during 4-year natural progression was evaluated. The baseline periodontal disease related and caries related factors were calculated, including number of teeth with bone loss > 50%, number of missing molars, number of teeth with widened periodontal ligament space (WPDL), number of teeth with periapical lesions and etc. Characteristics of populations with various number of tooth loss and the related factors that affected higher rate of tooth loss were analyzed. RESULTS: In 4 years of natural progression, 103 teeth were lost, and annual tooth loss per person was 0.12±0.38. Nine patients lost 3 or more teeth. Thirty-four patients lost 1 or 2 teeth, and 174 patients were absent of tooth loss. Molars were mostly frequent to lose, and canines presented a minimum loss. The number of teeth with WPDL, with periapical lesions, with intrabony defects, with probing depth (PD)≥7 mm, with PD≥5 mm, with clinical attachment loss≥5 mm, with bone loss > 50% and with bone loss > 65% were positively correlated to number of tooth loss. Results from orderly multivariate Logistic regression showd that the number of teeth with bone loss > 50% OR=1.550), baseline number of molars lost (OR=1.774), number of teeth with WPDL (1 to 2: OR=1.415; ≥3: OR=13.105), number of teeth with periapical lesions (1 to 2: OR=4.393; ≥3: OR=9.526) and number of teeth with caries/residual roots (OR=3.028) were significant risk factors related to higher likelihood of tooth loss and multiple tooth loss. CONCLUSION In 4 years of natural progression, the number of teeth with bone loss > 50%, baseline number of missing molars, number of teeth with WPDL, baseline number of teeth with periapical lesions and number of teeth with caries/residual roots were significantly related to higher risk of tooth loss and multiple tooth loss among Chinese young and middle-aged patients with severe periodontitis in rural areas.
Humans ; Tooth Loss/etiology* ; Periodontitis/complications* ; Tooth ; Periodontal Diseases ; Molar

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Humans ; Fasciitis/pathology* ; Fibroma/pathology* ; Gene Rearrangement ; Proto-Oncogene Proteins/genetics* ; Ubiquitin Thiolesterase

AIM: To explore the clinical efficacy of different anti-vascular endothelial growth factor(VEGF)drugs in the treatment of diabetic macular edema(DME), and analyze their relationship with optical coherence tomography(OCT)classification.METHODS: A total of 45 DME patients treated with ranibizumab(admitted to our hospital from February 2020 to February 2022)were selected as the ranibizumab group, and 45 DME patients treated with conbercept during the same period were selected as the conbercept group. The ranibizumab group was treated with retinal photocoagulation combined with ranibizumab, and the conbercept group was treated with retinal photocoagulation combined with conbercept. The improvement of symptoms(improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage), levels of serum interleukin-6(IL-6)and VEGF, central macular thickness(CMT), best corrected visual acuity(BCVA), and complications were compared between the two groups, and the relationship between their clinical efficacy and different OCT types were analyzed.RESULTS: There was no significant difference in the improvement time of macular edema, time of retinal thickness returning to normal, disappearance time of neovascularization and absorption time of fundus hemorrhage between the two groups(P>0.05); After treatment, the values of IL-6, VEGF and BCVA in the two groups were significantly lower than those before treatment(P<0.01), but there was no significant difference between the two groups(P>0.05); compared with before treatment, CMT was significantly decreased in both groups after treatment(P<0.05), and compared with ranibizumab group, the CMT was significantly decreased in the conbercept group(P<0.01); there was no significant difference in the incidence of complications between two groups(P>0.05); there were significant differences in the total effective rate among patients with serous retinal detachment(SRD), cystoid macular edema(CME)and diffuse retinal thickening(DRT; P<0.05), among which DRT had the highest total effective rate and SRD had the lowest total effective rate.CONCLUSION: Both conbercept and ranibizumab in the treatment of DME can effectively improve the clinical symptoms of patients and reduce the inflammatory response, but conbercept can better reduce the level of CMT, and has better treatment effect on DRT-type DME patients.

Seven compounds were isolated from Onychium japonicum by macroporous resin, silica gel, ODS, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were identified by NMR, MS and other spectroscopic methods as onychone A (1), quercetin (2), quercetin-3-O-α-L-rhamnoside (3), kaempferol-7-O-β-D-glucopyranoside (4), kaempferol-3-O-α-L-rhamnopyranoside (5), (-)-prunin (6), and norathyriol (7). Compound 1 is a novel macrocyclic flavonoid, and all the others are reported from this plant for the first time. In vitro cytotoxic activities of compounds 1-7 were evaluated by MTS testing with five cancer cell lines. Compound 7 exhibited weak cytotoxicity against tumor cell lines A549, SMMC-7721, and SW480.