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*

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Objective:To evaluate the clinical and prognostic value of prothrombin time(PT)and activated partial thromboplastin time(APTT)in newly diagnosed patients with multiple myeloma(MM).Methods:The clinical data of 116 newly diagnosed MM patients in the Second Hospital and Third Hospital of Shanxi Medical University from October 2014 to March 2022 were analyzed retrospectively,and the patients were divided into two groups:normal PT and APTT group and prolonged PT or APTT group.The differences in sex,age,classification,staging,bleeding events,laboratory indicators[including hemoglobin(Hb),platelet count(PLT),serum calcium,serum albumin(ALB),lactate dehydrogenase(LDH),serum creatinine and β 2-microglobulin],and cytogenetic characteristics between the two groups of patients were compared.The effect of prolonged PT or APTT on survival of patients with MM was analyzed.Results:Compared with patients in normal PT and APTT group,patients in prolonged PT or APTT group were more likely to experience bleeding events(x2=5.087,P=0.024),with lower ALB levels(x2=4.962,P=0.026)and PLT levels(x2=4.309,P=0.038),and higher serum calcium levels(x2=5.056,P=0.025).The positive rates of del17p,del13q and 1q21+in prolonged PT or APTT group were higher than those in normal PT and APTT group,but the difference was not statistically significant(P＞0.05).K-M survival analysis showed that the prolonged PT or APTT group had a shorter median progression-free survival(PFS)(P=0.032)and overall survival(OS)(P=0.032).Multivariate Cox analysis showed that prolonged PT or APTT(HR=2.1 16,95％CI:1.025-4.372,P=0.043)and age ≥65 years(HR=2.403,95％CI:1.195-4.836,P=0.014)were independent risk factor for OS in newly diagnosed MM patients.However,prolonged PT or APTT had no significant effect on PFS of newly diagnosed MM patients(HR=1.162,95％CI:0.666-2.026,P=0.597).Conclusion:Newly diagnosed MM patients with prolonged PT or APTT have worse clinical indicators,shorter PFS and OS.Prolonged PT or APTT is an independent risk factor for OS in MM patients.

Numerous studies have indicated that organic fertilizers (OFer) might contain heavy metals (HMs) that present health risks to organic farmers (OFar). This study compared the concentrations of six HMs (Zn, Ni, Cd, Cu, Pb, Cr) in the blood of two distinct groups of farmers: 30 OFar from a designated organic area in eastern Taiwan, and 74 conventional farmers (CFar) from neighboring non-organic designated regions. The findings revealed that the OFar exhibited higher levels of Zn (1202.70 ± 188.74 μg/L), Cr (0.20 ± 0.09 μg/L), and Ni (2.14 ± 1.48 μg/L) in their blood compared to the CFar (988.40 ± 163.16 μg/L, 0.18 ± 0.15 μg/L, and 0.77 ± 1.23 μg/L), respectively. The disparities in Zn, Cr, and Ni levels were measured at 214.3 μg/L, 0.02 μg/L, and 1.37 μg/L, respectively. Furthermore, among the OFar, those who utilized green manures (GM) displayed significantly elevated blood levels of Zn (1279.93 ± 156.30 μg/L), Cr (0.24 ± 0.11 μg/L), and Ni (1.94 ± 1.38 μg/L) compared to individuals who exclusively employed chemical fertilizers (CFer) (975.42 ± 165.35 μg/L, 0.19 ± 0.16 μg/L, and 0.74 ± 1.20 μg/L), respectively. The differences in Zn, Cr, and Ni levels were measured at 304.51 μg/L, 0.05 μg/L, and 1.20 μg/L, respectively. As a result, OFar should be careful in choosing OFer and avoid those that may have heavy metal contamination.

Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance of skin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring epidermal homeostasis, hair regeneration, and the repair of epidermal injuries. Recent studies have placed a growing emphasis on G protein-coupled receptor (GPCR) in the context of understanding epidermal stem cells, uncovering its significant role in determining their fate. The activation of GPCR triggers the subsequent dissociation of the βγ subunits from the α subunit of G protein, leading to the modulation of various downstream signaling pathways, such as the WNT-BMP signaling crosstalk and the Gαs-PKA signaling pathway. These pathways collectively influence the fate of epidermal stem cells. Consequently, targeted GPCR therapy has emerged as a promising strategy for improving skin health by orchestrating the fate of epidermal stem cells, unveiling potential therapeutic targets that demand further investigation.
Humans ; Stem Cells/cytology* ; Receptors, G-Protein-Coupled/physiology* ; Animals ; Epidermal Cells/physiology* ; Signal Transduction ; Epidermis/physiology* ; Skin/cytology*

OBJECTIVE: To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms. METHODS: Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the sham group, TAO model group, Compound Danshen Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the sham group were injected with sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish TAO mouse model. After modeling, mice in the sham and TAO model groups were intragastrically administered 0.5% (w/v) sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging. The pathological changes and thrombosis of the femoral artery were observed by morphological examination. The expressions of tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), endothelin-1 (ET-1), interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were detected by a fully automated biochemical analyzer. RESULTS: TXL promoted the restoration of blood flow in the lower limbs, reduced the area of thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1, IL-6, IL-1β, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01). CONCLUSIONS TXL had a protective effect on TAO mice, and the mechanism may involve inhibition of thrombosis and inflammatory responses. TXL may be a potential drug for the treatment of TAO.
Mice ; Male ; Animals ; Thromboangiitis Obliterans/chemically induced* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Thrombosis

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*

Objective: Patients with schizophrenia are living at the border of society and their sexuality is often neglected. The aim of the study is to explore the association among The Brief Psychiatric Rating Scale (BPRS), quality of life (QoL), Taiwanese Depression Questionnaire, and Sexual Desire Inventory in people with schizophrenia (PwS). Methods: This study used a cross-sectional design with 277 psychiatric inpatients. A descriptive analysis, difference analysis, and logistic regression model were presented to identify relevant variables that may affect the probability of good QoL. Results: The study showed that male PwS had higher scores of standard deviation (SD) than females in PwS. The study also showed that smoking, early illness onset age, and shorter illness duration demonstrated a significantly higher SD. The logistic regression analysis showed that BPRS, depression, and SD significantly affected the probability of QoL. By structural equation model, SD would be positively correlated with mental status and SD would indirectly influence QoL. Conclusion Our results showed psychological and sociological factors interactions may contribute to the QoL and SD for PwS. This study also demonstrated a close relationship between SD, depression, and BPRS. These factors may predict the probability of good life quality for the PwS.