OBJECTIVE: To investigate the variability of bone metabolism levels among different populations and its association with knee osteoarthritis (KOA) pain. METHODS: A total of 50 people (control group) who participated in physical examination from January 2023 to June 2023 were selected, including 26 males and 24 females, wtih a mean aged of (52.14±9.04) years old ranging 41 to 65 years old. The other 50 patients with knee osteoarthritis(case group) who attended the outpatient clinic of the Orthopedics and Traumatology Department in the same time period, including 19 males and 31 females, with a mean age of (53.60±7.76) years old ranging 40 to 65 years. The two groups of Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC) and bone metabolism markers, such as 25-hydroxy-cholecalciferol[25(OH)D], β-isomerized typeⅠcollagen C-telopeptide breakdown products (β-CTX), total typeⅠprocollagen N-terminal propeptide (t-PINP), osteocalcin (OC), parathormone (PTH) levels were compared. Pearson correlation analysis was used to compare the correlation between two groups of bone metabolism related markers and WOMAC. RESULTS: The WOMAC score of the case group (39.90±2.34) was higher than that of the control group (3.60±0.57), with significant difference (P<0.05). There was no significant difference between the two groups of 25 (OH)D, β-CTX and PTH (P>0.05). The t-PINP and OC of the case group were (62.90±52.40) and (19.88±10.15) ng·ml-1, respectively, and those of the control group were (38.86±10.82) and (14.90±3.62) ng·ml^-1, respectively;the t-PINP and OC of the case group were higher than those of the control group, with significant difference (P<0.05). Pearson correlation analysis showed that t-PINP was positively correlated with WOMAC pain score in the case group (r²=0.045, P<0.01). CONCLUSION Bone metabolism levels in the serum of patients with knee osteoarthritis are different from those of healthy people, and the difference between OC and t-PINP is the most obvious, and the concentration of t-PINP levels is positively correlated with pain symptoms in patients with KOA. However, the specific mechanism of correlation between the bone metabolism levels of patients with KOA and their pain symptoms needs to be further elucidated by basic experimental research as well as by enlarging the samples.
Humans ; Female ; Male ; Middle Aged ; Osteoarthritis, Knee/metabolism* ; Aged ; Adult ; Bone and Bones/metabolism* ; Pain/etiology* ; Biomarkers/metabolism*

OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent

OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis.Methods The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed,2 patients were lost to follow-up at 10 months after surgery,at the final 22 cases were included in the study,including 13 males and 9 females with an average age of(52.00±6.89)years old,were treated with one-stage posterior lesion removal and internal spinal fixation.The operation time,intraoperative bleeding,follow-up time,ery-throcyte sedimentation rate(ESR)and C-reactive protein(CRP)before and after operation were recorded.The pain visual ana-logue scale(VAS),Oswestry disability index(ODI),the Japanese Orthopaedic Association(JOA)score for neurofunction,American Spinal Injury Association(ASIA)spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy.Results All patients were followed up from 12 to 30 months with an average of(17.41±4.45)months.The operation time was 70 to 155 min with an average of(1 16.59±24.32)min;the intraoperative bleeding volume was 120 to 520 ml with an average of(275.00±97.53)ml.CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than pre-operative levels(P＜0.05).VAS,JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results(P＜0.05).There was no significant difference between ASIA preoperative and 1 week after operation(P＞0.05),and a significant difference between preoperative and last follow-up(P＜0.05).In the final follow-up,21 patients had ex-cellent efficacy,1 patient had fair,and there was no recurrence during the follow-up.Conclusion One-stage transpedicular le-sion removal and internal spinal fixation,with few incisions and short operation time,helps the recovery of neurological func-tion,and the prognosis meets the clinical requirements,which can effectively control Brucella spondylitis.

Abnormal cell apoptosis is closely related to the occurrence of hematologic tumors, B-cell lymphoma-2 (BCL-2), as a key anti-apoptotic protein in intrinsic programmed cell death, has become a hot spot in the treatment of hematologic tumors in recent years. Venetoclax is an oral small-molecule selective BCL-2 inhibitor approved by the Food and Drug Administration (FDA） for the treatment of chronic lymphocytic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) patients and for the treatment of elderly acute myeloid leukemia (AML) patients that is not suitable for aggressive chemotherapy. In addition, it also showed a promising clinical application in treatment of non-Hodgkin's lymphoma (NHL) patients, which is a new expansion of the clinical indications for venetoclax. In this review, the role of BCL-2 protein family played in the regulation of NHL cell apoptosis, the development of BCL-2 inhibitors and the recent research progress of venetoclax in the treatment of NHL are reviewed.
Aged ; Antineoplastic Agents/therapeutic use* ; Apoptosis Regulatory Proteins ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Hematologic Neoplasms/drug therapy* ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Lymphoma, B-Cell ; Lymphoma, Non-Hodgkin/drug therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Sulfonamides

OBJECTIVE Only limited number of drugs are currently available for treating ischemic stroke. Therapeu?tic angiogenesis has recently emerged as one of the most promising therapies for cerebral ischemic injury. Isopropyl-β-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (IDHP) is a metabolite derived from the botanical formulation for Dantonic?. Here, we investigated the angiogenic efficacy of IDHP in cerebral ischemia. METHODS The in vivo effects of IDHP were evaluated in the C57BL/6 mouse Matrigel plug and rat transient middle cerebral artery occlusion (tMCAO) models. Primary human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC) were used to explore the effects of IDHP on stimulating proliferation, migration and tube formation in vitro. ELISA and Western blotting were used to quantitate the release and expression of relevant target molecules and signaling path?ways. RESULTS IDHP reduced infarct volume and improved sensorimotor function in rats subjected to tMCAO by pro?moting angiogenesis, and promoted Matrigel neovascularization in mice. Moreover, IDHP produced a biphasic modula?tion on proliferation and migration both in HUVEC and HBMEC. It also induced tube formation in a 12-day HUVEC-HDF co-culture model and in Matrigel assays. IDHP-induced angiogenesis was accompanied by increased levels of p-AMPKα (Thr172) and p-eNOS (Ser1177) both in vitro and in vivo, and the decreased level of VEGF in rat brains on day 1 whereas enhanced level of VEGF on day 3 and 7 after tMCAO. Mechanistically, AMPK knockdown or pharmacologi?cally inhibiting AMPK and its upstream kinases (CaMKKβ) inhibited the eNOS phosphorylation induced by IDHP in HUVEC. Furthermore, selective eNOS inhibitor (L-NIO), selective CaMKKβ inhibitor (STO) and AMPKa inhibitor (Com?pound C) blocked the capillary-like tube formation in the co-culture model induced by IDHP (10 nmol · L-1). CONCLU?SION Collectively, these findings showed that IDHP protected rats from cerebral ischemia-reperfusion injury by promot?ing angiogenesis via activating CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling, and suggest it to be a promising new drug candidate for the prevention and/or treatment of cerebral ischemia and other vascular occlusive diseases.

Pneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust, usually as the result of certain occupations. The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis, which can eventually lead to death caused by respiratory and/or heart failure. Pneumoconiosis is widespread globally, seriously threatening global public health. Its high incidence and mortality lie in improper occupational protection, and in the lack of early diagnostic methods and effective treatments. This article reviews the epidemiology, safeguard procedures, diagnosis, and treatment of pneumoconiosis, and summarizes recent research advances and future research prospects.
Dust ; Humans ; Occupational Diseases ; Occupational Exposure ; Pneumoconiosis/epidemiology* ; Pulmonary Fibrosis

An UPLC-MS/MS method was developed to simultaneously determine complanatoside A and complanatoside B in rat plasma with rutin as the internal standard and applied to examine the effect of salt-processing on pharmacokinetics of these two flavonoid glycosides. The pharmacokinetic parameters were estimated using DAS 3.2.6 and subjected to independent sample t-test with SPSS 23.0. No significant difference in T_(max) of complanatoside B was observed between the raw and processed groups; however, in the processed group, C_(max) and AUC_(0-12 h) of complanatoside B increased obviously(P<0.05), while MRT_(0-12 h) decreased from(3.34±0.44) h to(1.81±0.36) h(P<0.05). C_(max) [(14.72±11.13) μg·L~(-1)] and MRT_(0-24) [(3.93±0.26) h] of complanatoside A in the raw group were statistically different from those [(35.64±21.99) μg·L~(-1),(1.43±0.24) h] in the processed group(P<0.05). As a result, salt-processing can facilitate the in vivo adsorption and accelerate the excretion of complanatoside A and complanatoside B.
Animals ; Astragalus Plant ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Glycosides ; Rats ; Semen ; Tandem Mass Spectrometry

Objective::To study on the content change and transformation rule of eight main characteristic components in stir-frying process of Glycyrrhizae Radix et Rhizoma. Method::The contents of liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid and glycyrrhetinic acid in Glycyrrhizae Radix et Rhizoma were determined simultaneously by HPLC. The chromatographic conditions were Waters Symmetry® C₁₈ column (4.6 mm×250 mm, 5 μm), and the mobile phase of acetonitrile (A)-0.05%phosphoric acid solution (B) for gradient elution (0-9 min, 19%-25%A; 9-18 min, 25%-34%A; 18-38 min, 34%-51%A; 38-58 min, 51%-89%A), the flow rate of 1 mL·min^-1, the detection wavelengths at 320 nm (0-16 min), 276 nm (16-25 min), 370 nm (25-28 min), 254 nm (28-58 min), the injection volume of 10 μL and the column temperature at 30 ℃. Result::After stir-frying, the total content of three components with dihydroflavone as mother nucleus was decreased, while the total content of three components with chalcone as mother nucleus showed an upward trend, the content change of glycyrrhizic acid was not obvious, but glycyrrhetinic acid content showed a slight upward trend. When the monomer heating temperature reached 130 ℃, dihydroflavones and chalcones could be isomerized with each other, and with the increase of temperature, the isomerization became more obvious. When the heating temperature rose to 180 ℃ (isoliquiritin apioside was 130 ℃), in addition to the isomerization, the glucosidic bond of flavonoid glycosides began to break and gradually transformed into the corresponding secondary glycosides or aglycones. Glucosidic bond of glycyrrhizic acid could also be broken to form glycyrrhetinic acid, which was detected at 150 ℃. Conclusion::The change of chemical composition is complex during stir-frying process of Glycyrrhizae Radix et Rhizoma, in addition to the isomerization and glucosidic bonds breaking observed in this experiment, there may be other complex reactions. The content of one compound in the herb is affected by many factors during its processing, such as the time and temperature of frying, the stability of the compound itself and so on.