Stepwise treatment strategy for spontaneous osteonecrosis of the medial femoral condyle of the knee joint / 中国组织工程研究

BACKGROUND:Currently,there have been a variety of conservative and surgical treatment plans for spontaneous osteonecrosis of the knee,achieving excellent results.However,a broad consensus on indication and guide of surgical treatment has not been announced.In clinical practice,there is still a misunderstanding that unicondylar replacement or total knee arthroplasty should be performed upon the discovery of spontaneous osteonecrosis of the knee,while an urgent need for universal access to the concept of stepwise therapy. OBJECTIVE:To summarize and find the factors leading to the poor effect of conservative treatment in spontaneous osteonecrosis of the knee,which occurred on the medial femoral condyle,from the literature and clinical cases,at the same time,combined with the Koshino stage,to propose the strategy of stepwise spontaneous osteonecrosis of the knee treatment on the medial femoral condyle. METHODS:A systematic search of the literature database was conducted to summarize the factors leading to poor outcomes of conservative treatment in spontaneous osteonecrosis of the medial femoral condyle.Meanwhile,according to the Clinical&Health Records for analytics&Sharing system,the cases receiving conservative and surgical treatment in spontaneous osteonecrosis of the medial femoral condyle in the Department of Orthopedics of Guangdong Provincial Hospital of Chinese Medicine from January 2017 to January 2023 were analyzed retrospectively,then the causes of success and failure in typical cases were summarized and analyzed. RESULTS AND CONCLUSION:(1)Early diagnosis and treatment of spontaneous osteonecrosis of the knee were very important for prognosis.For sudden knee pain in some patients,if no obvious abnormality was found in the X-ray examination,and the symptoms persisted and could not be relieved for more than 1 week,an MRI examination was recommended to detect early spontaneous osteonecrosis of the knee.(2)The X-ray images of Koshino stage 1 and stage 2 of spontaneous osteonecrosis of the medial femoral condyle were difficult to be distinguished,which needed to be probed by MRI.MRI images of Koshino stage 1 were mainly characterized by bone marrow edema,and an osteonecrosis area with a clear boundary was not formed,while MR images of Koshino stage 2 showed a necrotic area with a clear boundary.(3)Five factors leading to the poor effect of conservative treatment on spontaneous osteonecrosis of the medial femoral condyle were summarized:a.The necrotic area was＞5 cm2;b.The necrotic area accounted for more than 40%of the condyle;c.relative compression percentage of medial meniscus≥33%(with or without medial meniscus injury and subchondral bone marrow edema);d.MRI depth of necrotic area(anterior-posterior diameter of sagittal necrotic area)＞20 mm;e.varus deformity of lower limb＞6°.(4)Conservative treatment of spontaneous osteonecrosis of the knee in Koshino stage 1 was good.For spontaneous osteonecrosis of the knee in Koshino stage 2,conservative treatment was preferred or combined with drilling decompression.If there was no relief or improvement of symptoms or in MRI after 3 months,while the patient had any of the previous five factors,then knee preservation surgery should be considered.For spontaneous osteonecrosis of the knee in Koshino stage 3 and stage 4,knee preservation surgery should be selected based on the previous five factors,including age,gender and activity level of the patient.Total knee arthroplasty was used for spontaneous osteonecrosis in Koshino stage 4,which was associated with symptomatic patellofemoral arthritis,valgus alignment,or necrotic area,which greatly affected the stability of unicondyle prosthesis.

Research progress of IDO1-mediated tryptophan metabolism in sepsis / 药学学报

Sepsis is a condition characterized by organ dysfunction resulting from the systemic inflammatory response triggered by an infection. Excessive inflammation and immunosuppression are intertwined, and severe cases may even develop into multiple organ failure. Studies have shown that indoleamine 2,3-dioxygenase 1-mediated tryptophan metabolism is involved in the occurrence and development of sepsis, and elevated plasma kynurenine levels and Kyn/Trp ratios are early indicators of sepsis development. In this paper, we provide a comprehensive summary of the role of IDO1 in the acute inflammatory phase of sepsis, late immunosuppression, and organ damage. This includes its regulation of inflammatory state, immune cell function, blood pressure, and other aspects. Additionally, we analyze preclinical studies on targeted IDO1 drugs. An in-depth understanding and study of IDO may help to understand the pathogenesis and clinical significance of sepsis and multiple organ damage from a new perspective and provide new research ideas for exploring its prevention and treatment methods.

Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023) / 中华创伤杂志

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Value of combined model based on clinical and radiomics features for predicting invasiveness of lung adenocarcinoma manifesting as ground glass nodule / 医疗卫生装备

Objective To evaluate the predictive value of a combined model based on clinical and radiomics features for the invasiveness of lung adenocarcinoma manifesting as ground glass nodule(GGN).Methods Clinical data of patients with GGN-type lung adenocarcinoma who underwent chest CT and were confirmed by surgical pathology at some hospital from January to December 2019 were analyzed retrospectively,and the extraction of imaging histological features was performed using Python-based open resource Pyradiomics.A clinical model was constructed based on independent risk factors obtained from univariate and multivariate analyses,a radiomics model was built using the screened radiomics features,and a combined model was established with the predictive values of the clinical models and radiomics scores(Radscore).The predictive performance of the three models in the training and test sets was assessed using ROC curves,the statistical significance of the differences in the ROC curves of the three models for predicting GGN-type lung adenocarcinoma was assessed using the Delong test,and the net benefits of the models were analyzed using clinical decision curves.Results Logistic multifactor analysis showed that age(P=0.020 2)and vascular characteristics(P=0.002 2)were the independent predictors of the degree of the invasiveness of lung adenocarcinoma.The AUCs of the radiomics model,clinical model and combined model were 0.876,0.867 and 0.904 on the training set,and 0.828,0.828 and 0.864 on the test set,respectively.The difference between the ROC curves of the combined model and the clinical and radiomics models was not statistically significant(P>0.05)on the test set.Clinical decision curves showed a higher clinical benefit when using the combined model to predict the invasiveness under most conditions of threshold probability.Conclusion The combined model based on clinical and radiomics features enhances the predictive performance for the invasiveness of GGN-type lung adenocarcinoma.

Effect of Tongsai granules on airway epithelial barrier in a rat model of acute exacerbation of chronic obstructive pulmonary disease and role of EGFR/ERK signaling pathway / 中国病理生理杂志

AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.

Analysis of allergen profiles in dust mite-sensitive allergic rhinitis patients in Dalian / 中国医科大学学报

Objective To investigate the allergen profiles of dust mite-sensitive allergic rhinitis patients in Dalian,and to lay the foun-dation for precise prevention and control of allergic rhinitis.Methods Clinical data of allergic rhinitis patients treated at Affiliated Zhongshan Hospital of Dalian University from January 2015 to December 2022 were collected.The allergen distribution spectrums were compared between different groups designated according to sex,age,allergen reaction level,combination of other allergens,and testing time.Results A total of 1 330 allergic rhinitis patients were included,among whom the total detection rate of dust mite allergy was 60.83%(n= 809),with 330(40.79%)of these having dust mite sensitization alone and 479(59.21%)having multiple sensitization.There were many kinds of allergens in multiple sensitization.Among those with dust mite allergy,all 20 combined allergens detected in this group were analyzed,and mugwort,cat hair,and common rinea grass were the top three allergens in combined sensitization,accounting for 64.52%.The number of other allergens combined with dust mite was mainly 1-3 species(88.73%),and a maximum of 10 allergens were simultaneously present.Patients with 1-3 other combined sensitivities were mainly reactive to respiratory allergens,and those with 4 or more allergens essentially had joint sensitization to respiratory and food allergens.As for the allergen reaction level,the dust mite sensitivity reaction was relatively strong,with grade 3 or above accounting for 61.19%.Except for mugwort,the other combined allergens elicited mainly grade 1 and grade 2 reactions.The detection rates of dust mite allergy were 61.84%in male patients and 59.94%in female patients,with no statistical difference between the sexes(χ2=4.000,P= 0.261).The detection rate of dust mite sensitization was highest in the group aged<20 years and decreased with age(χ2=69.984,P<0.001).Dust mite-sensitive allergic rhinitis mainly occurred from August to October,and the detection rate of dust mite sensitization was the highest in October,reaching 80.16%.Conclusion The dust mite sensitization rate in patients with allergic rhinitis in the Dalian area is relatively high,and multiple sensitization is more common.Combinations of respiratory allergens mainly involve 1-3 types,and mugwort,cat hair,and common ragweed are the most common aller-gens combined with dust mite.Therefore,prevention and control of allergic rhinitis should focus on the characteristics of dust mite allergy in this region.

Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction / 南方医科大学学报

OBJECTIVE@#To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability.@*METHODS@#A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1βwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry.@*RESULTS@#The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1β (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01).@*CONCLUSION@#SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

PAFR/Stat3 axis maintains the symbiotic ecosystem between tumor and stroma to facilitate tumor malignancy

Stroma surrounding the tumor cells plays crucial roles for tumor progression. However, little is known about the factors that maintain the symbiosis between stroma and tumor cells. In this study, we found that the transcriptional regulator-signal transducer and activator of transcription 3 (Stat3) was frequently activated in cancer-associated fibroblasts (CAFs), which was a potent facilitator of tumor malignancy, and formed forward feedback loop with platelet-activating factor receptor (PAFR) both in CAFs and tumor cells. Importantly, PAFR/Stat3 axis connected intercellular signaling crosstalk between CAFs and cancer cells and drove mutual transcriptional programming of these two types of cells. Two central Stat3-related cytokine signaling molecules-interleukin 6 (IL-6) and IL-11 played the critical role in the process of PAFR/Stat3 axis-mediated communication between tumor and CAFs. Pharmacological inhibition of PAFR and Stat3 activities effectively reduced tumor progression using CAFs/tumor co-culture xenograft model. Our study reveals that PAFR/Stat3 axis enhances the interaction between tumor and its associated stroma and suggests that targeting this axis can be an effective therapeutic strategy against tumor malignancy.

Metabolic profile changes of kidney aging and protective effects of Polygonatum sibiricum polysaccharides on D-galactose-induced aging mice / 数字中医药（英文）

Objective@#To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). @*Methods@#A total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. @*Results@#Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). @*Conclusion@#Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

Diagnosis and Treatment of Traditional Chinese Medicine for Encephalopathy Based on the Theory of “Identificating the Onset of Diseases” / 中医杂志

Brain diseases in traditional Chinese medicine were complex and difficult to diagnosis and treatment， and new diagnostic and therapeutic ideas are urgently needed. The onset of the disease was the result of the struggle between healthy qi and pathogenic qi. Common types of the onset of diseases included sudden onset， slow onset， latent onset， secondary onset， and recurrent onset， reflecting the strength of the healthy qi and pathogenic qi， the pathogenic qi that reduced diseases， the site of onset， and other informatin. “Identificating the onset of diseases” was simple and easy to operate， and helped to clarify the complex development of encephalopathy. When applying it， we should first identify urgency and importance， focus on the characteristics； grasp the tendency of diseases， and know the overall situation of the disease； compare similarities and differences horizontally； and carefully observe and dynamically understand the disease. “Identificating the onset of diseases” has the characteristics of comprehensiveness and prognosis， and can lay the foundation for pattern identification and treatment and “treating disease before its onset”.

Health and functional outcome of whole body vibration for children and adolescents with cerebral palsy: a systematic review using WHO-FICs / 中国康复理论与实践

ObjectiveTo construct a research framework for systematic review of health and functional outcomes of whole body vibration training in children and adolescents with cerebral palsy based on the theory and method of World Health Organization Family of International Health Classifications (WHO-FICs), and to systematically review the major health conditions and physical functions, intervention programs of whole body vibration training, and health and functional outcomes of vibration intervention in children and adolescents with cerebral palsy. MethodsBased on the WHO-FICs method, the PICO architecture of systematic reviews was constructed, and the databases of CNKI, Wanfang Data, PubMed, Web of Science, EBSCO, and Embase were searched to collect randomized controlled trials about the health and functional effects of whole body vibration training on children and adolescents with cerebral palsy from the establishment to September 30th, 2022, and a systematic review was conducted. ResultsEight articles, seven in English and one in Chinese, from five countries, were included, mainly from journals in clinical rehabilitation, neurorehabilitation, physical medicine and rehabilitation, etc., published mainly after 2010, involving 227 participants (three to 12.3 years old). The quality of the articles was evaluated using the Physical Therapy Evidence Database scale with a mean score of six. The ICD-11 codes included 08 diseases of the nervous system, 8D20 spastic cerebral palsy, 8D20.1 spastic bilateral cerebral palsy, 8D20.10 spastic quadriplegia cerebral palsy and 8D2Z unspecified cerebral palsy. The primary functioning of cerebral palsy was characterized as muscle spasticity, abnormal skeletal development, joint deformities and muscle weakness, decrease of selective motor control and gait abnormalities; for the activity and participation, the functioning included walking difficulties, decrease of mobility and weight loading, and low levels of physical activities. The main intervention was whole body vibration, in postures of lying, squatting or standing, mainly standing, in the mode of vertical vibration. The frequency was 5 to 30 Hz, and the amplitude was below 9 mm, three to five times a week for eight weeks to six months. The intervention settings include medical institutions, schools and families; mainly for therapeutics and recovery. The health and health-related outcomes were mainly involved s7 structures related to movement, b710 mobility of joint functions, b730 muscle power functions, b735 muscle tone functions, b760 control of voluntary movement functions, d410 changing basic body position, d415 maintaining a body position, d450 walking, d455 moving around, and d420 transferring oneself; such as improvements of neuromusculoskeletal and joint functions, muscle spasm, static balance, muscle strength, and control of movement, the control of body posture and walking, range of activities and self-care. ConclusionWhole body vibration training is effective on cerebral palsy, mainly in standing position, 5 to 30 Hz, and amplitude below 9 mm; three to five times a week for eight weeks to six months. The outcomes of whole body vibration training are mainly reflected in the improvement of body-motor functions, and activity and participation.

Efficiency and safety analysis of Plerixafor combined with granulocyte colony-stimulating factor on autologous hematopoietic stem cell mobilization in lymphoma / 中华血液学杂志

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin's lymphoma (8.7%) , 11 cases of follicular non-Hodgkin's lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt's lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.

Shikonin induces hepatocellular carcinoma cell apoptosis by suppressing PKM2/PHD3/HIF-1α signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the mechanism of shikonin-induced death of human hepatocellular carcinoma SMMC-7721 cells.@*METHODS@#Cultured SMMC-7721 cells and normal hepatocytes (L-02 cells) were treated with 4, 8, or 16 μmol/L shikonin, and the changes in cell viability was assessed using MTT assay. The levels of ATP and lactic acid in the cell cultures were detected using commercial kits. Co-immunoprecipitation and immunofluorescence staining were used to determine the relationship among pyruvate kinase M2 (PKM2), prolyl hydroxylase 3 (PHD3), and hypoxia-inducible factor-1α (HIF-1α). The expressions of PHD3, PKM2, HIF-1α, Bax, cleaved caspase-3, and Bcl-2 in SMMC-7721 cells were detected with Western blotting, and cell apoptosis was analyzed with annexin V-FITC/PI staining. The effects of RNA interference of PKM2 on PHD3 and HIF-1α expressions in SMMC-7721 cells were detected using Western blotting.@*RESULTS@#The IC50 of shikonin against SMMC-7721 and L-02 cells was 8.041 μmol/L and 31.75 μmol/L, respectively. Treatment with shikonin significantly inhibited the protein expressions of PKM2, HIF-1α and PHD3 and nuclear translocation of PKM2 and HIF-1α in SMMC-7721 cells. Coimmunoprecipitation and immunofluorescence staining confirmed that shikonin inhibited the formation of PKM2/PHD3/HIF-1α complex and significantly reduced the contents of lactic acid and ATP in SMMC-7721 cells (P < 0.05). The expressions of PHD3 and HIF-1α decreased significantly after PKM2 knockdown (P < 0.05). Shikonin treatment significantly increased the apoptosis rate, enhanced the expressions of Bax and cleaved caspase-3, and decreased Bcl-2 expression in SMMC-7721 cells (P < 0.05).@*CONCLUSIONS@#Shikonin induces apoptosis of SMMC-7721 cells possibly by inhibiting aerobic glycolysis through the PKM2/PHD3/HIF-1α signaling pathway to cause energy supply dysfunction in the cells.

Clinical features and imaging manifestations in 10 patients with genetically diagnosed adult-onset neuronal intranuclear inclusion disease / 中华神经医学杂志

Objective:To summarize the clinical and imaging features of 10 patients with genetically diagnosed neuronal intranuclear inclusion disease (NIID) to avoid clinical misdiagnosis and mismanagement of NIID.Methods:Ten patients with NIID, admitted to our hospital from January 2020 to March 2022, were chosen in our study. All patients were confirmed as having NIID by NOTCH2NLC gene assay. Their clinical data, gene detection results and skin pathological results were collected and anlyzed. Results:These patients aged from 57 to 84 years, including 8 females. The episodic symptoms as main symptoms were noted in 6 patients, including 3 patients with encephalopathy, 1 patient with TGA, 1 patient with stroke-like episode, and 1 patient with migraine-like symptoms. Chronic progressive symptoms as main symptoms were noted in 4 patients, including 3 patients with dementia and 1 patient with Parkinson's disease. There were characteristic linear hyper-intensities in diffusion weighted imaging (DWI) in the corticomedullary junction predominantly in the frontal lobes. White matter lesions appeared in T2 Flair might have been noted years before lesions appeared in DWI, with wider ranges. All had GGC repeated expansion in NOTCH2NLC gene in non-coding area, with mutation number>60. Skin biopsy was performed in 6 patients, showing the formation of intranuclear inclusion bodies in different cells; and ubiquitin and P62 were found positive in immunohistochemical staining. Conclusions:NIID patients have large clinical heterogeneity; most patients have episodic symptoms as main manifestations, often accompanied by chronic progressive symptoms; stroke attack and migraine are rare clinical phenotypes of NIID. The high signal at the cortical medullary junction in DWI is a characteristic imaging change.

Correlation analysis between trace element levels and carotid atherosclerosis / 中风与神经疾病杂志

@#To analyze the correlation between trace element levels and carotid atherosclerosis（CAS），explore the risk factors of CAS. Methods People who underwent physical examination，and performed carotid artery ultrasonography，trace element detection and inflammatory factors detection were collected from January 2020 to February 2022 in the Physical Examination Center of the First Hospital of Jilin University. 325 cases were selected in strict accordance with the inclusion and exclusion criteria，the subjects were classified into two groups according to carotid intima-media thickness（IMT）. There were 146 cases in the normal carotid artery group and 179 cases in the carotid atherosclerosis group. Chi-square test，t test and rank sum test were used to compare the differences in basic information，serum trace element levels，C-reactive protein（CRP） and blood biochemistry between the two groups；Spearman correlation analysis was used to explore the correlation between carotid IMT and trace elements，CRP and inflammatory factors；multivariate Logistic regression was used to analyze the risk factors of CAS；all tests were performed on two sides，and the difference was statistically significant at P<0.05.Results （1）The age，waist circumference，carotid IMT，systolic blood pressure，prevalence rate of diabetes，the ratio of smoking，drinking and male in the carotid atherosclerosis group were higher than those in the normal carotid artery group，and the difference was statistically significant（P<0.05）. （2）There were statistical differences（P<0.05） in the contents of CRP，iron，zinc，LDL-C，FBG and UA between the normal carotid artery group and the carotid atherosclerosis group. The contents of CRP，iron，LDL-C，FBG and UA in the carotid atherosclerosis group were higher than those in the normal carotid group，and the zinc content in the carotid atherosclerosis group was lower than that in the normal carotid artery group. （3）Carotid IMT was positively correlated with age，waist circumference，systolic blood pressure，diastolic blood pressure，iron，CRP，triglycerides，LDL-C，fasting blood glucose，uric acid，while negatively correlated with zincand ratio of zinc and copper. （4）Multivariate Logistic regression analysis of carotid atherosclerosis，the results showed that age，gender，the ratio of smoking，the ratio of drinking，CRP，zinc，LDL-C，and fasting blood glucose were risk factors for carotid atherosclerosis，and zinc was a protective factor for carotid atherosclerosis. Conclusion Trace element iron is positively correlated with carotid IMT，and the higher its level is，the higher the risk of CAS；the trace element zinc is negatively correlated with carotid IMT，and the higher its level is，the lower the risk of CAS is；zinc is a protective factor for CAS.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

A comparison of binocular and monocular surgery on the effect of eye-covering pretreatment on emergence delirium after general anesthesia in pre-school aged children / 中国实用护理杂志

Objective:To evaluate the effect of eye-covering pretreatment on acute delirium in ophthalmology preschool-age children who underwent binocular and monocular surgery by general anesthesia.Methods:The 300 preschool-age children who underwent general anesthesia of elective ophthalmic surgery in the Second Affiliated Hospital, Zhejiang University School of Medicine, from August 2019 to February 2021 were selected as the research object. They were divided into control group and blindfold group with 150 cases each by random number-table. Children in the control group received regular education on cartoon animation videos before surgery; children in the blindfold group received eye-covering pretreatment on the basis of cartoon animation videos(monocular surgery with monocular cover, binocular surgery with binocular cover). The Modified Yale Preoperative Anxiety Scale (m-YPAS) , the Nursing Delirium Screening Scale(NU-DESC), the incidence rate of delirium and the score of postoperative nursing difficulty were compared between two groups.Results:The 271 cases were completed in this study, including 129 cases(monocular surgery 66 cases, binocular surgery 63 cases) in the blindfold group and 142 cases (monocular surgery 73 cases, binocular surgery 69 cases) in the control group. The preoperative m-YPAS score, the postoperative NU-DESC score, the incidence rate of acute delirium and postoperative nursing care difficulty score of monocular surgery in the blindfold group , monocular surgery was (40.28 ± 15.02) points, 1.00 (0.00, 2.00) points, 27.3%(18/66), 1.00 (1.00, 2.00) points,and binocular surgery was (41.69 ± 16.35) points, 1.00 (0.00, 2.00), 39.7%(25/63), 1.00(1.00, 2.00); in the control group, monocular surgery was (46.28 ± 15.76) points, 2.00 (1.00, 3.00) points, 67.1% (49/73), 2.00 (1.00, 3.00) points, and binocular surgery was (47.77 ± 14.82) points, 3.00 (2.00, 4.00) points, 82.6% (57/69) and 2.00 (1.50, 3.00) points respectively. The difference between the two groups was statistically significant ( t= -2.29, -2.24, Z values were -5.74 - -2.95, χ2= 32.94, 25.78, all P<0.05). The preoperative m-YPAS score, the postoperative NU-DESC score, the incidence rate of acute delirium and postoperative nursing care difficulty score of monocular surgery patients in the blindfold group had no significantly statistical difference with that of binocular surgery patient (all P>0.05) . Conclusions:Monocular/ binocular eye-covering pretreatment can effectively decrease the preoperative m-YPAS score, the postoperative NU-DESC score, incidence rate of acute delirium and the postoperative nursing care difficulty in preschool-age children who underwent general anesthesia both monocular or binocular surgery. There was no difference in the application effect of monocular or binocular surgery.

Efficacy analysis of transfusion of suspended RBCs and washed RBCs in patients with positive direct Coombs testing results / 中国输血杂志

【Objective】 To compare the efficacy and safety of transfusion of suspended RBCs and washed RBCs in patients with positive direct Coombs testing results. 【Methods】 A retrospective analysis was conducted on 98 patients with positive direct Coombs testing results as 2+ or less in the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2020. Among them, 31 patients, from January 2015 to December 2016, were transfused with washed RBCs and set as the control group; the other 67 patients, from January 2017 to December 2020, transfused with suspended RBCs, were enrolled as the experimental group. The changes of main laboratory indexes and the incidence of transfusion adverse reactions before and after transfusion of 2 U and 4 U RBCs were compared between the two groups to evaluate the efficacy and safety of transfusion. 【Results】 After 2 U and 4 U transfusion, Hb increased by 12±4.967 (g/L) and 23.78±12.736 (g/L) in the control group, while 12.85±7.109 (g/L) and 22.68±9.832 (g/L) in the experimental group, All transfusions of the two groups were effective, and no significant differences in Hb, TBIL, IBIL and LDH were noticed by groups (P>0.05). No significant difference in the incidence of adverse reactions to blood transfusion between the 2 groups was observed (P>0.05). 【Conclusion】 The transfusion of suspended RBCs is safe and effective in patients with positive direct Coombs testing results as 2+ or less, and the transfusion of washed RBCs was unnecessary.

Progress in application of genetically engineered mice exposed to cigarette smoke in research on drug targets and pathogenesis of COPD / 中国药理学通报

Chronic obstructive pulmonary disease (COPD) is a common illness of respiratory system, seriously threatening human life and health. Emergence and development of COPD are results of inter-actions between genes and pathogenic factors. The combination of cigarette smoking exposure and genetically engineered mice is able to make similar biological effects of special genes under pathogenic condition of cigarette smoke exposure. The article summarizes the method practice on study of drug targets, inflammation and immune in COPD, analyzes the results of these studies, and describes the basic process of the method, aiming to provide reference for research on pathogenesis and drugs of COPD.

Preparation and in vitro characterization of remdesivir-loaded liposomes for inhalation / 中国药科大学学报

@#Remdesivir-loaded liposomes for inhalation were prepared and the in vitro properties were evaluated. Firstly, preparation methods of remdesivir-loaded liposomes were screened, and single-factor experiments were conducted to optimize the prescription and preparation process. Then the physical property, deposition ratio and aerodynamic particle size distribution of remdesivir-loaded liposomes suspension for inhalation were comprehensively evaluated. As a result, the optimal liposomes were prepared by the thin-film dispersion method with pH 6.5 phosphate-buffered saline as the hydration medium. In the prescription, the ratio of drug to DPPC was 1∶20; the cholesterol accounted for 10% of total lipids; and 20% DSPE-mPEG 2000 was added as stabilizer.4% trehalose was added as lyoprotectant when lyophilizing to obtain ideal appearance, good stability and a small particle size change after reconstitution. Remdesivir-loaded liposomes were spherical with smooth surface and uniform particle size distribution under transmission electron microscope. In vitro release tests showed no significant change for release curves of remdesivir-loaded liposomes suspension before and after nebulization. Deposition experiments indicated that the fine particles fraction of liposomes was 51.4%, and the mass median aerodynamic diameter was less than 5 μm measured by next generation impactor. To sum up, remdesivir-loaded liposomes for inhalation with high encapsulation efficiency and stability can achieve a suitable particle size distribution to effectively deposit in the lung after nebulization, which provides a new approach for the treatment of COVID-19.