Objective:To explore the effect of ubiquitin-specific protease 42(USP42)on osteogenic differentiation of human adipose-derived stem cells(hASCs)in vivo and in vitro.Methods:A combina-tion of experiments was carried out with genetic depletion of USP42 using a lentiviral strategy.Alkaline phosphatase(ALP)staining and quantification,alizarin red S(ARS)staining and quantification were used to determine the osteogenic differentiation ability of hASCs under osteogenic induction between the experimental group(knockdown group and overexpression group)and the control group.Quantitative re-verse transcription PCR(qRT-PCR)was used to detect the expression levels of osteogenesis related genes in the experimental group and control group,and Western blotting was used to detect the expression levels of osteogenesis related proteins in the experimental group and control group.Nude mice ectopic im-plantation experiment was used to evaluate the effect of USP42 on the osteogenic differentiation of hASCs in vivo.Results:The mRNA and protein expressions of USP42 in knockdown group were significantly lower than those in control group,and those in overexpression group were significantly higher than those in control group.After 7 days of osteogenic induction,the ALP activity in the knockdown group was sig-nificantly higher than that in the control group,and ALP activity in overexpression group was significantly lower than that in control group.After 14 days of osteogenic induction,ARS staining was significantly deeper in the knockdown group than in the control group,and significantly lighter in overexpression group than in the control group.The results of qRT-PCR showed that the mRNA expression levels of ALP,os-terix(OSX)and collagen type Ⅰ(COL Ⅰ)in the knockdown group were significantly higher than those in the control group after 14 days of osteogenic induction,and those in overexpression group were signifi-cantly lower than those in control group.The results of Western blotting showed that the expression levels of runt-related transcription factor 2(RUNX2),OSX and COL Ⅰ in the knockout group were significant-ly higher than those in the control group at 14 days after osteogenic induction,while the expression levels of RUNX2,OSX and COL Ⅰ in the overexpression group were significantly lower than those in the control group.Hematoxylin-eosin staining of subcutaneous grafts in nude mice showed that the percentage of osteoid area in the knockdown group was significantly higher than that in the control group.Conclusion:Knockdown of USP42 can significantly promote the osteogenic differentiation of hASCs in vitro and in vi-vo,and overexpression of USP42 significantly inhibits in vivo osteogenic differentiation of hASCs,and USP42 can provide a potential therapeutic target for bone tissue engineering.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To explore the influence of Buqi Qingchang Decoction(composed of Buzhong Yiqi Decoction plus Baitouweng Decoction with Curcumae Radix and Curcumae Longae Rhizoma added)combined with XELOX chemotherapy and Bevacizumab targeted therapy on the clinical efficacy,quality of life and survival period of patients with metastatic colorectal cancer of qi deficiency and damp-heat syndrome.Methods A retrospective study was conducted in 70 patients with metastatic colorectal cancer of qi deficiency and damp-heat syndrome who were admitted to the Department of Oncology,Chongqing Hospital of the First Affiliated Hospital of Guangzhou University of Chinese Medicine(Chongqing Beibei District Hospital of Traditional Chinese Medicine)from December 2020 to December 2023.The patients were divided into an observation group and a control group according to the therapy,with 35 cases in each group.The control group was treated with XELOX chemotherapy combined with Bevacizumab targeted therapy,while the observation group was given oral administration of Buqi Qingchang Decoction together with chemotherapy and targeted therapy.The changes in the serum levels of tumor markers such as carcinoembryonic antigen(CEA)and carbohydrate antigen 199(CA199),and Karnofsky Performance Status(KPS)scores for quality of life in the two groups were observed before and after treatment.Moreover,the clinical efficacy,progression-free survival(PFS)and overall survival(OS)were compared between the two groups.Results(1)After treatment,the objective response rate(ORR)and disease control rate(DCR)in the observation group were 51.42％(18/35)and 85.71％(30/35),respectively,which were significantly higher than those in the control group[25.71％(9/35)and 54.29％(19/35),respectively],and the differences between the two groups were statistically significant(P＜0.05 or P＜0.01).(2)The PFS of the observation group was 16.7 months and that of the control group was 12.9 months,and the OS of the observation group was 23.3 months and that of the control group was 17.7 months.The PFS and OS of the observation group were significantly longer than those of the control group,and the differences were statistically significant(P＜0.05 or P＜0.01).(3)After treatment,the levels of serum CEA and CA199 in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05).The decrease of serum CEA and CA1 99 levels and the increase of KPS scores in the observation group were superior to those in the control group,and the differences were statistically significant(P＜0.05).Conclusion XELOX chemotherapy and Bevacizumab regimen combined with Buqi Qingchang Decoction exerts certain effect in treating metastatic colorectal cancer.The combined therapy is effective on enhancing the efficacy to a certain extent,prolonging the survival period of patients,reducing the risk of disease progression,decreasing the levels of serum tumor markers,and improving the quality of life of patients.

Objective To investigate the clinical efficacy of Shen Jiang Zhouche Powder(composed of modified Lizhong Pill,Erchen Decoction,and Zhouche Pill)in the treatment of malignant pleural effusion(MPE)patients with fluid retention in the chest and hypochondrium syndrome.Methods Eighty MPE patients with fluid retention in the chest and hypochondrium syndrome were randomly divided into the treatment group and the control group,with 40 cases in each group.Both groups were given conventional western medical treatment,and additionally the control group was treated with Spironolactone and Furosemide Tablets orally while the treatment group was treated with Shen Jiang Zhouche Powder orally.A total of 21 days constituted one course of treatment,and both groups were treated for two courses and then were followed up for one month.The changes of traditional Chinese medicine(TCM)syndrome scores,scores of Karnofsky Performance Status(KPS)established by Eastern Cooperative Oncology Group(ECOG),and scores of self-rating scale of sleep(SRSS)in the two groups were observed before and after treatment.After treatment,the clinical efficacy,TCM syndrome efficacy and clinical safety of the two groups were evaluated.Results(1)After treatment and one-month follow-up,the total clinical effective rate in the treatment group was 67.5%(27/40)and that in the control group was 45.0%(18/40),and the intergroup comparison(by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that in the control group(P＜0.05).(2)After two courses of treatment,the total effective rate of TCM syndrome improvement in the treatment group was 92.5%(37/40)and that of the control group was 50.0%(20/40),and the intergroup comparison(by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.01).(3)After treatment,except for the score of dyspnea in the control group,the scores of each of the main symptoms(including dry cough,chest tightness,chest pain,tightness of breath,dyspnea)and accompanied symptoms as well as the total TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05 or P＜0.01),and the decrease of the scores of each of the main symptoms and accompanied symptoms as well as the total TCM syndrome scores were significantly superior to those in the control group(P＜0.05 or P＜0.01).(4)After treatment,the scores of KPS and SRSS in the two groups were significantly improved compared with those before treatment(P＜0.01),and the improvement in the treatment group was significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)There were no obvious adverse reactions occurring in both groups,while only mild symptoms of the adverse reactions were presented.The incidence of adverse reactions in the treatment group was 7.5%(3/40)and that in the control group was 12.5%(5/40),and the difference was not statistically significant between the two groups(P＞0.05).Conclusion Shen Jiang Zhouche Powder exerts certain clinical efficacy in the treatment of MPE patients with fluid retention in the chest and hypochondrium syndrome,which is effective on alleviating the clinical symptoms of TCM,and improving the quality of life of patients,without obvious toxicity or side effects.

This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.
Mice ; Animals ; Imiquimod ; Drugs, Chinese Herbal/pharmacology* ; Glycyrrhizic Acid ; Chromatography, High Pressure Liquid/methods*

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.
Animals ; Rats ; Arachidonic Acid ; Biomarkers/blood* ; Blood Proteins ; Chromatography, High Pressure Liquid ; Creatinine ; Drugs, Chinese Herbal/therapeutic use* ; Glomerulonephritis/metabolism* ; Metabolomics ; Urea ; Chronic Disease ; Disease Models, Animal ; Complex Mixtures/therapeutic use*

Objective: To review the clinical characteristics, to illustrate diagnosis and management experience of orbital and cranial complications of pediatric acute rhinosinusitis. Methods: The clinical data of 24 children with orbital and cranial complications of acute rhinosinusitis who received endoscopic sinus surgery combined with drug treatment in Beijing Children's Hospital from January 2017 to December 2021 were retrospectively reviewed. There were 19 boys and 5 girls. The age varied from 13 to 159 months, with a median 47.5 months. The following diagnoses were obtained: 12 isolated subperiosteal orbital abscess, 2 associated with preseptal abscess, 2 associated with intraorbital abscess, 7 associated with optic neuritis, and 1 associated with septic cavernous sinus thrombosis. Clinical characteristics, organism isolated and outcomes were analyzed through descriptive methods. Results: All 24 patients presented with fever; 9 presented with nasal congestion and purulent discharge. The clinical manifestations of orbital infection included orbital edema, pain, proptosis and displacement of globe in all patients, while visual impairment was recognized in 7 children. Purulent drainage was cultured in 17 patients, among which 12 were positive. All patients underwent nasal endoscopic surgical interventions uneventfully, excluding one patient who required a second surgical procedure. Follow-up period ranged from 5 to 64 months. All patients resolved fully, with the exception of 2 children who got permanent blindness with visual loss preoperative. There was no recurrence or death. Conclusions: Orbital and cranial complications of pediatric acute rhinosinusitis could be severe with an occult onset. For patients with vison impairment, any signs of intracranial complications and a lack of response to conservative management, an urgent endoscopic intervention is needed.
Male ; Female ; Child ; Humans ; Abscess/therapy* ; Retrospective Studies ; Sinusitis/therapy* ; Orbital Cellulitis ; Acute Disease ; Exophthalmos ; Orbital Diseases/therapy*

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.
Male ; Child ; Female ; Humans ; Immunoglobulins, Intravenous/therapeutic use* ; Blood Coagulation ; COVID-19 ; China/epidemiology* ; Connective Tissue Diseases ; Coronary Aneurysm ; Fever ; Systemic Inflammatory Response Syndrome/therapy*

Chinese medicine self-assembly nano-strategies（CSAN） is to utilize the self-assembly property of Chinese medicine components， so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions， and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics， and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine， which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine， which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy， and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time， traditional Chinese medicine（TCM） has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly， but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy， improve the targeting of drugs， enhance the anti-tumor efficacy， and reduce the side effects of chemotherapy， which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple， low cost， and has better safety than traditional nano-preparations， which is conducive to the promotion of the clinical transformation of nano-preparations， and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore， based on a large number of researches in this field in recent years， this paper reviewed the formation mechanism， different assembly forms， formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure（CNKI）， PubMed， WanFang data and VIP， and summarized the application of CSAN in different tumor therapies， providing a reference for further research on CSAN.

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ²=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ ²=82.26,P<0.001;χ²=114.01,P<0.001;χ²=82.26,P<0.001) and accuracy (χ²=20.27,P<0.001;χ²=15.56,P<0.001;χ²=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ²=17.01,P<0.001;χ²=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.
Humans ; Lymphatic Metastasis/diagnostic imaging* ; Retrospective Studies ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/surgery* ; Tomography, X-Ray Computed ; Ultrasonography/methods*