Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Informed consent is an important ethical symbol in clinical research,and researchers have the responsibility to fully inform participants of the research information before conducting clinical research.However,it is difficult to obtain complete informed consent form participants or their guardians within a narrow treatment time period in clinical research conducted in emergency situations.Currently,in addition to traditional general informed consent,there are also reality-accepted informed consent,including exemption of informed consent,broad informed consent,and deferred informed consent.By introducing the origin and development process of deferred informed consent in clinical research,this paper sorted out the current application status of deferred informed consent,proposed the prerequisites for applying deferred informed consent in emergency situations,and explored the issues that need to be noted during the application process of deferred informed consent.It is hoped to provide an ethical defense and ethical procedure for the application of deferred informed consent in clinical research in emergency situations.

Objective: To explore the current status and associated factors of bullying behavior among middle school students in Shanghai, so as to provide a reference basis for carrying out bullying intervention work. Methods: From May to June 2021, a stratified cluster sampling method was used to select 19 000 middle school students from 63 schools in 16 districts of Shanghai, and the Shanghai Youth Health Risk Behavior Survey Questionnaire was used to conduct an anonymous questionnaire survey of enrolled students. Chi square test and binary Logistic regression analysis were employed to investigate the associated factors of bullying among middle school students. Results: The prevalence of bullying behaviors in Shanghai was 15.5%, with males and junior high school students exhibiting the higher reporting rate(19.5%,17.2%). And malicious teasing or name calling had the highest reported rate at 9.4%. The results of binary Logistic regression analysis showed that fighting ( OR =5.02), attempting to smoke ( OR =3.22), having a feeling of sadness and hopelessness ( OR =2.50) and getting drunk( OR =1.72) were positively associated with bullying behavior among middle school students. Fighting ( OR =3.83-8.97), attempting to smoke ( OR =2.92-5.52), having a feeling of sadness and hopelessness ( OR =2.40-4.34), and getting drunk ( OR =1.66-2.34) were positively correlated with 6 forms of bullying (malicious teasing or name calling, intentionally damaging someone else s belongings, deliberately excluding someone from activities or isolating someone, threatening or intimidating others, hitting, kicking, or pushing someone, and verbally harassing or attacking someone online) ( P <0.05). Conclusions Bullying behavior of middle school students in Shanghai primarily presents as verbal harassment. In the future, greater attention should be directed towards bullies, and it should recognize potential hazards promptly and implement precise intervention measures.

Objective To investigate the clinical characteristics of Ureaplasma urealyticum(UU)infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia(BPD).Methods A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology,Shenzhen Maternity and Child Healthcare Hospital,from September 2018 to September 2022.According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization,the subjects were divided into three groups:UU-negative group(155 infants),UU infection group(70 infants),and UU colonization group(33 infants).The three groups were compared in terms of general information and primary and secondary clinical outcomes.Results Compared with the UU-negative group,the UU infection group had significant increases in the incidence rate of BPD,total oxygen supply time,and the length of hospital stay(P<0.05),while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group(P>0.05).Conclusions The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU(i.e.,infection or colonization),and there are significant increases in the incidence rate of BPD,total oxygen supply time,and the length of hospital stay in extremely preterm infants with UU infection.UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.

The patient,a 42-year-old male,with a history of hepatitis B and membranous nephropathy,had inter-mittent fever and chills 12 days before admission.In the first 2 days after admission,the patient's condition aggra-vated with redness,swelling and pain in the left scrotum and perineum.Immediate surgical debridement was per-formed.The patient had a persistent low fever,with blood and pus cultures showing Candida albicans positive,thus was diagnosed fungal necrotizing fasciitis and pyomyositis.The patient was treated with echinocandins mica-fungin(150 mg,qd)for antifungal infection,and was given encroaching dressing change,hyperbaric oxygen thera-py,nutritional support,etc.Two months after surgery,the patient's condition improved and he was discharged.The early clinical symptoms of necrotizing fasciitis and pyomyositis caused by Streptococcus spp.infection lack spe-cificity,thus are prone to be delayed.For patients with concomitant immune diseases,attention should be paid to the prevention and early treatment of complex infection.The appropriate selection of empirical antifungal agents at the early stage has clinical significance.

Objective:To analyze the risk factors for late-onset hemorrhagic cystitis(LOHC)after allogeneic hematopoietic stem cell transplantation(allo-HSCT),the risk factors for the progression of LOHC to severe LOHC,and the effect of LOHC on survival.Methods:The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed.The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis.Then,the differences in overall survival(OS)and progression-free survival(PFS)between different groups were analyzed.Results:The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows:age≤45 years old(P=0.039),intensified conditioning regimen with fludarabine/cladribine and cytarabine(P=0.002),albumin ≤ 30 g/L on d30 after transplantation(P=0.007),CMV-DNA positive(P=0.028),fungal infection before transplantation(P=0.026),and the occurrence of grade Ⅱ-Ⅳ aGVHD(P=0.006).In the transplant patients who have already developed LOHC,the occurance of LOHC within 32 days after transplantation(P=0.008)and albumin ≤ 30 g/L on d30 after transplantation(P=0.032)were independent risk factors for the progression to severe LOHC.The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC(P=0.041).Conclusion:For the patients aged ≤ 45 years old and with intensified conditioning regimen,it is necessary to be vigilant about the occurrence of LOHC;For the patients with earlier occurrence of LOHC,it is necessary to be vigilant that it develops into severe LOHC.Early prevention and treatment of LOHC are essential.Regular monitoring of CMV-DNA and albumin levels,highly effective antiviral and antifungal therapies,and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.

Objective:To analyze the risk factors of primary poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myeloid malignancies and the impact of primary PGF on survival. Methods:The clinical data of 146 patients with myeloid malignancies who underwent allo-HSCT in our hospital from January 2015 to December 2021 were retrospectively studied. Some relevant clinical parameters which may affect the development of primary PGF after allo-HSCT were selected for univariate and multivariate analysis,as well as performed survival analysis. Results:A total of 9 patients (6.16％) were diagnosed with primary PGF,and their medium age was 37(28-53) years old. Among them,1 case underwent matched sibling donor HSCT,1 case underwent matched unrelated donor HSCT,and 7 cases underwent HLA-haploidentical related donor HSCT. Moreover,5 cases were diagnosed as cytomegalovirus (CMV) infection,and 3 cases as Epstein-Barr virus (EBV) infection. Univariate and multivariate analysis showed that CD34+cell dose<5×106/kg and pre-transplant C-reactive protein (CRP)>10 mg/L were independent risk factors for occurrence of the primary PGF after allo-HSCT in patients with myeloid malignancies. The 3-year overall survival (OS) rate of primary PGF group was 52.5％,which was significantly lower than 82.8％ of good graft function group (P<0.05). Conclusion:Making sure pre-transplant CRP≤10 mg/L and CD34+cell dose ≥5×106/kg in the graft may have an effect on preventing the occurrence of primary PGF after allo-HSCT. The occurrence of primary PGF may affect the OS rate of transplant patients,and early prevention and treatment are required.

Objective:To construct a quality prediction and diagnosis model for fully automatic blood cell analyzers based on equipment characteristics,and to explore its application value in dynamic quality management and control of fully automatic blood cell analyzers.Methods:Based on the characteristics of the equipment,the quality prediction and diagnosis model for automatic blood cell analyzer was constructed by using the Long Short Term Memory(LSTM)model and Softmax classifier and Adam optimization algorithm,and 18 equipment characteristics parameters were designed as input variables to predict and diagnose 10 common quality problems.The data of five automatic blood cell analyzers in clinical use in the Laboratory Center of the First Affiliated Hospital of Xinjiang Medical University from 2021 to 2022 were selected as samples for model training and testing,and the prediction accuracy and diagnostic accuracy of the model were evaluated,and the auxiliary effect of quality management of five automatic blood cell analyzers from January to June 2023 was observed with the model output results.The performance of the quality prediction and diagnosis model was evaluated by accuracy and precision,and the reduction in the average number of weekly failures before and after the model-assisted quality management of the fully automatic blood cell analyzer was compared.Results:The model was applied to the prediction diagnosis of five devices,and the prediction accuracy rates were 97.5%、95.9%、96.3%、95.3%and 95.2%,respectively,and there was no significant difference in the prediction and diagnosis accuracy of the five devices(P>0.05).The diagnostic accuracy was 92.6%、89.7%、91.1%、92.4%,and 91.1%,respectively,with no statistically significant difference(P>0.05).The predictive diagnostic accuracy of the five devices was 92.6%,89.7%,91.1%,92.4%and 91.1%,respectively,and there was no significant difference in the predictive diagnostic accuracy of the five devices(P>0.05).After applying the model to assist the quality management control of five devices,the average weekly failure rate decreased by 67.35%,68.36%,69.72%,68.97%,and 67.47%,respectively.Conclusion:The quality prediction and diagnosis model of the fully automatic blood cell analyzer based on equipment characteristics can accurately predict equipment quality problems according to the equipment characteristic values,correctly diagnose the causes of quality problems and propose corresponding treatment measures.It can be applied to equipment quality management and control to effectively reduce the failure rate and is suitable for different equipment.