Exploration of signaling pathways with unclear action status and possible effects on related diseases or functions after knockdown of silencing information regulator 1 gene in chondrocytes / 中国组织工程研究

BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip? Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.

Construction of porous structure on the surface of PLLA/β-tricalcium scaffold and its effect on cell adhesion / 西安交通大学学报(医学版)

【Objective】 To construct a 3D printed PLLA/β-tricalcium (PLLA/β-TCP) bone tissue engineering scaffold surface porous structure through simple treatment with NaOH solution, increase the roughness and hydrophilicity of the scaffold, and promote cell adhesion on the scaffold surface. 【Methods】 The PLLA/β-TCP mesh scaffold was prepared by 3D printing melt deposition molding technology, and the scaffold was roughed by NaOH etching. The effects of NaOH concentration and time on the scaffold were observed according to the microstructure, energy spectrum, contact angle, mechanics, and cell adhesion of the scaffold. 【Results】 The PLLA/β-TCP composite scaffold constructed by melt deposition technology had a pre-set porous structure, and the pores were interconnected. After NaOH etching, a porous structure with both macroscopic and microscopic pores was formed. The increase in any of the NaOH concentration and time parameters would lead to the increase of pore diameter and surface roughness. When the NaOH treatment parameter was 0.1 mol/L (9 h), it could significantly reduce the water contact angle on the surface of the scaffold, and had no significant effect on the compressive strength of the scaffold. In vitro cell testing showed that the surface porous composite scaffold etched with NaOH had more advantages in the adhesion and proliferation of BMSCs. 【Conclusion】 Using NaOH to process 3D printing of PLLA/β-TCP bone tissue engineering scaffolds can effectively improve the surface morphology of the scaffold, and optimize its hydrophilicity and cell adhesion.

Improving the surface hydrophilicity and performance of 3D printed PCL/β-TCP mesh support by sodium hydroxide alkali etching method / 西安交通大学学报(医学版)

【Objective】 To solve the problem of insufficient hydrophilicity on the surface of polycaprolactone (PCL)/β-TCP bone tissue engineering scaffolds, NaOH etching method was used to improve the surface microstructure of 3D printed PCL/β-TCP scaffolds, further affecting their hydrophilicity and cell response. 【Methods】 PCL/β-TCP mesh scaffolds were prepared using 3D printing melt deposition molding technology, and the surface roughness of the scaffolds was modified by NaOH etching. The effects of two reaction parameters, NaOH concentration and time, on the microstructure, spectral elements, contact angle, compressive strength, and cell adhesion of the scaffolds before and after modification were observed. 【Results】 After NaOH etching, the surface microporous structure of the mesh scaffold was successfully prepared. With the increase of either NaOH concentration or time, the surface micropores of the scaffold increased while the contact angle of the material surface decreased. However, the compression strength of the etched scaffold treated with NaOH for 1 mol/L (24 h) or 10 mol/L (6 h) was not statistically significant compared to the untreated group (P>0.05). The number of cells on the etched scaffold increased, with a larger spreading area of individual cells, making it more advantageous in the adhesion and proliferation of BMSCs. 【Conclusion】 The use of NaOH etching to improve the hydrophilicity of 3D printed PCL/β-TCP bone tissue engineering scaffolds is a low-cost and effective strategy which can effectively improve the wettability and cell adhesion of the scaffolds.

Preparation of tripterygium glycoside nanoparticles and therapeutic effect on arthritis rats / 中国药理学通报

Aim To prepare tripterygium glycoside nanoparticles and probe into their therapeutic effect on collagen-induced arthritis ( CIA) rats. Methods Tripterygium glycosides polyglycoside nanoparticles were prepared by thin film dispersion method and their quality was assessed. The CIA model was established and drug intervention performed. The body weight, toe swelling degree and arthritis index were measured. The pathological changes of the organs, knee and ankle synovium were observed. The serum levels of kidney function and inflammatory cytokine expression were detected in rats. Results The prepared tripterygium wil-fordii polyglycoside nanoparticles were round particles with uniform distribution and stable properties under electron microscope. Compared with the model group, the swelling of the left and right toes of medication group significantly decreased (P < 0. 01), and the ar-thritis index markedly decreased ( P < 0. 01). Among them, the efficacy of the TG-NPs group was better than that of the TG group. Compared with the normal group, the indexes of heart, spleen, kidney and testis all significantly decreased (P <0. 05, P<0.01). TG-NPs group had a significantly reduced pathological ankle-joint injury in knee cartilage and increased apoptotic synovial cells. Compared with the model group, the serum levels of ALT and BUN and CRE in TG-NPs group were significantly lower (P < 0. 05 ), and IL-1β, TNF-α and IL-6 levels decreased significantly (P <0. 05). Conclusions TG-NPs have good therapeutic effect on CIA through induction of synovial cell apoptosis and decrease of the expression of inflammatory cytokines. By intravenous injection of blood circula-tion, slow and controlled release of drugs can be achieved, the first pass effect caused by oral drug can be avoided, the viscera toxicity can be reduced, which provides an experimental basis for the development of new nanoagents for the treatment of rheumatoid arthritis.

Diagnostic value of HPV-DNA typing combined with serum NLR and DCLK1 for cervical cancer / 中国现代医生

@#Objective To investigate the value of receiver operating curve human papilloma virus(HPV)-DNA typing combined with serum neutrophil lymphocyte ratio(NLR)and bicorticoid kinase 1(DCLK1)levels in the early diagnosis of cervical cancer.Methods A total of 120 patients with early cervical cancer diagnosed in our obstetrics and gynecology department from August 2018 to June 2022 were randomly included as cervical cancer group,and 120 patients with benign lesions were included as benign group.The level of DCLK1 was detected by ELISA;NLR was detected by automatic blood cell analyzer;HPV subtypes in cervical secretions were detected by HPV genotyping gene chip detection system;the cut-off values of serum NLR and DCLK1 levels in the diagnosis of cervical cancer were analyzed by using the receiver operator curve(ROC);four table method was applied to analyze the diagnostic value of HPV-DNA typing,serum NLR,DCLK1 levels alone and in combination for cervical cancer.Results Compared with benign group,the levels of serum NLR and DCLK1 in cervical cancer group were obviously higher(P<0.05).The positive rate of HR-HPV in cervical cancer group was obviously higher than that in benign group(P<0.05).The ROC curve was drawn with serum NLR and DCLK1 levels as test variables,the results showed that the AUC of serum NLR and DCLK1 predicting early cervical cancer was 0.724 and 0.718,respectively,and the cut-off value was 3.08 and 3.32,respectively.HPV-DNA typing combined with serum NLR and DCLK1 detected 18 false positives and 17 false negatives,Kappa value was 0.725,which was consistent with pathological results.The sensitivity,negative predictive value and accuracy of HPV-DNA typing combined with serum NLR and DCLK1 levels in the diagnosis of early cervical cancer were obviously higher than those of HPV-DNA typing,serum NLR and DCLK1 levels alone(P<0.05).Conclusion The results of HPV-DNA typing combined with NLR and DCLK1 in the diagnosis of early cervical cancer are highly consistent with the pathological results,and the sensitivity and accuracy are obviously improved.

Effects of intranasal administration of tripterygium glycoside-bearing liposomes on behavioral cognitive impairment of mice induced by central nervous system inflammation / 中国中药杂志

Tripterygium glycosides liposome(TPGL) were prepared by thin film-dispersion method, which were optimized accor-ding to their morphological structures, average particle size and encapsulation rate. The measured particle size was(137.39±2.28) nm, and the encapsulation rate was 88.33%±1.82%. The mouse model of central nervous system inflammation was established by stereotaxic injection of lipopolysaccharide(LPS). TPGL and tripterygium glycosides(TPG) were administered intranasally for 21 days. The effects of intranasal administration of TPG and TPGL on behavioral cognitive impairment of mice due to LPS-induced central ner-vous system inflammation were estimated by animal behavioral tests, hematoxylin-eosin(HE) staining of hippocampus, real-time quantitative polymerase chain reaction(RT-qPCR) and immunofluorescence. Compared with TPG, TPGL caused less damage to the nasal mucosa, olfactory bulb, liver and kidney of mice administered intranasally. The behavioral performance of treated mice was significantly improved in water maze, Y maze and nesting experiment. Neuronal cell damage was reduced, and the expression levels of inflammation and apoptosis related genes [tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), BCL2-associated X(Bax), etc.] and glial activation markers [ionized calcium binding adaptor molecule 1(IBA1) and glial fibrillary acidic protein(GFAP)] were decreased. These results indicated that liposome technique combined with nasal delivery alleviated the toxic side effects of TPG, and also significantly ameliorated the cognitive impairment of mice induced by central nervous system inflammation.

Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Exploration of pathological technology training for professional postgraduates of pathology / 中华医学教育探索杂志

Combined with teaching practice, this study summarizes the teaching contents, methods and effect evaluation of pathological technology for professional postgraduates majoring in pathology. According to the basic conditions of postgraduates, the pathological technology training program has been formulated, student-centered heuristic teaching is carried out by using diversified teaching methods such as flipped classroom, interactive theoretical teaching is carried out by using the intelligent teaching platform, and practical teaching is carried out by using the problem-based learning mode, aiming to improve the theoretical literacy and practical level of pathological technology of professional postgraduates majoring in pathology, improve their clinical research thinking, and lay a foundation for clinical pathological diagnosis and scientific research in the future.

Comparative analysis of fractional CO 2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions / 中国医师杂志

Objective:To investigate the effects of fractional CO 2 laser, focused ultrasound and simple drug treatment of gynecological vulva white lesions. Methods:A prospective study was conducted on 126 patients with white lesions of the vulva admitted to Hainan Cancer Hospital from August 2018 to December 2020. They were divided into drug group, focused ultrasound group and fractional CO 2 laser group by random number table method, with 42 patients in each group. The drug group was treated with mometasone furoate cream or dexamethasone acetate cream, and the focused ultrasound group was treated with focused ultrasound; the fractional CO 2 laser group was treated with fractional CO 2 laser. The serum interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and human epidermal growth factor (EGF) levels before and after treatment, and Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI) scores of the three groups were compared. Results:Before treatment, there was no significant difference in the levels of IL-2, TNF-α, CRP and EGF among the three groups (all P>0.05). After treatment, the levels of IL-2, TNF-α, CRP and EGF in the three groups were significantly decreased, and the levels of IL-2, TNF-α, CRP and EGF in the focused ultrasound group and fractional CO 2 laser group were lower than those in the drug group, with statistically significant difference (all P<0.05). Before treatment, there was no significant difference in the white lesions, dry pruritus, sexual pain and chapped skin scores of the three groups (all P>0.05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO 2 laser were lower than those of the drug group, with statistical significance (all P<0.05). Before treatment, there was no significant difference in the scores of symptoms and feelings, daily activities and interpersonal relationship of the three groups (all P>0.05); After treatment, scores of all dimensions of the three groups were significantly decreased, and scores of all dimensions of the focused ultrasound group and fractional CO 2 laser were lower than those of the drug group, with statistical significance (all P<0.05). Conclusions:Fractional CO 2 laser has a remarkable effect in the treatment of gynecological vulva white lesions, which can reduce the level of inflammatory factors in patients, improve the pain condition, and improve the quality of life.

C2 pedicle screw insertion assisted by mobilization of the vertebral artery in cases with high-riding vertebral artery / 中华外科杂志

Objective: To examine the feasibility, safety, and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with high-riding vertebral artery (HRVA). Methods: The clinical data of 12 patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation in the Department of Neurosurgery, the First Affiliated Hospital of University of Science and Technology of China between January 2020 and November 2021 were retrospectively analyzed. All patients had high-riding vertebral artery on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 10 females aged (48.0±12.8) years (range: 17 to 67 years). After correction of vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including the anterior atlantodental interval (ADI), the distance of the odontoid tip above the Chamberlain line, the clivus-canal angle, were collected and compared by paired t-test. Results: Mobilization of the high-riding vertebral artery was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were achieved in all 12 patients. All patients achieved bone fusion 6 months after surgery. No looseness and shift in internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative ADI decreased from (6.1±1.9) mm to (2.0±1.2) mm (t=6.73, P<0.01), the distance of the odontoid tip above the Chamberlain line decreased from (10.4±2.5) mm to (5.5±2.3) mm (t=7.12, P<0.01), the clivus-canal angle increased from (123.4±11.1) ° to (134.7±9.6) ° (t=2.50, P=0.032), the JOA score increased from 13.3±2.1 to 15.6±1.2 (t=6.99, P<0.01). Conclusion: The C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

Analysis on early mobilization of acute ischemic stroke patients with different degrees of neurological impairment / 中华老年医学杂志

Objective:To understand the current situation of early mobilization in elder patients with acute ischemic stroke, and to analyze the influencing factors of early mobilization in patients with different degrees of neurological deficits, aiming to provide evidence for promoting early mobilization in patients with stroke and for formulating intervention strategies.Methods:Patients with acute ischemic stroke admitted to the stroke centers of two class A tertiary hospitals in Hunan Province between January and December 2021 were enrolled.The degree of neurological impairment, activities of daily living and muscle strength were evaluated within 24 hours after admission, and patients' performance of early mobilization was recorded.Based on whether patients performed out-of-bed activities such as sitting at the bedside, standing or walking, transferring from bed to chair within 48 hours after admission, they were divided into an early ambulation group and a non-early ambulation group.Univariate analysis and Logistic regression analysis were then used to examine the influencing factors of early ambulation in patients with mild to moderate neurological deficits.Results:Among 257 patients with acute ischemic stroke, 60.7%(156 cases)conducted early mobilization.The rate of early mobilization for patients with moderate neurological deficits was only 12.9%(12/193), significantly lower than that for patients with mild neurological deficits(87.8%, 144/164)( χ2=139.571, P<0.001).Univariate analysis showed that there were significantly differences in the level of activities of daily living, stroke history, strength of the upper and lower limbs of the affected side between the early and non-early ambulation groups with moderate neurological impairment(all P<0.05), and there were significant differences in the level of activities of daily living between the early ambulation group and the non-early ambulation group in patients with mild neurological impairment( χ2=11.907, P<0.001).Logistic regression analysis showed that requiring assistance in daily life( OR=4.189, 95% CI: 1.724-10.668, P=0.002), muscle strength of the affected lower extremity ≤ grade 3( OR=9.605, 95% CI: 2.627-35.113, P=0.001)and moderate neurological deficits( OR=8.585, 95% CI: 3.216-22.913, P<0.001)were the risk factors of early mobilization in stroke patients. Conclusions:The rate of stroke patients with moderate neurological impairment performing early mobilization is low within 48 hours after admission.Activities of daily living ability, limb muscle strength and degrees of neurological deficits are influencing factors of early mobilization in stroke patients.

Huanglian Jiedutang Treats Acute Gouty Arthritis via NLRP3 Inflammasome and TLR4/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of Huanglian Jiedutang on the inflammatory injury in the mouse model of acute gouty arthritis （AGA） and to explore the mechanism of Huanglian Jiedutang in treating AGA. MethodForty male C57BL/6J mice were randomized into blank， model， colchicine （0.83 mg·kg-1）， and Huanglian Jiedutang （5 g·kg-1） groups. The mouse model of AGA was established by injecting monosodium urate （MSU） crystals into the ankle joint. The swelling degree of the right ankle joint of each mouse was measured every day for 7 days， and the pathological changes of the ankle joint were detected by hematoxylin-eosin （HE） staining after 7 days. The other 40 C57BL/6J mice were grouped as above. After 18 hours of modeling， the right ankle joint was collected， and real-time polymerase chain reaction was employed to measure the mRNA levels of interleukin （IL）-1β， tumor necrosis factor （TNF）-α， IL-6， NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The expression levels of IL-1β， TNF-α， and IL-6 were measured by the enzyme-linked immunosorbent assay. Western blot was employed to determine the protein levels of NLRP3 inflammasome， Toll-like receptor 4 （TLR4）， and nuclear factor-κB （NF-κB）. ResultCompared with the blank group， the model group showed swelling right ankle joint （P<0.01）， obvious foreign body granuloma in the ankle joint with inflammatory cell infiltration. After the treatment with Huanglian Jiedutang， the ankle joint swelling was relieved （P<0.05， P<0.01）， and the size of foreign body granuloma was reduced. Compared with the blank group， the model group showed up-regulated mRNA levels of IL-1β， TNF-α， and IL-6 in the ankle joint tissue （P<0.01）， up-regulated mRNA levels of NLRP3 and Caspase-1 in the NLRP3 inflammasome （P<0.05， P<0.01）， and up-regulated protein levels of NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05， P<0.01）. Huanglian Jiedutang down-regulated the mRNA levels of IL-1β， TNF-α， IL-6， NLRP3， and Caspase-1 （P<0.05， P<0.01） and the protein levels of IL-1β， TNF-α， IL-6， NLRP3， Caspase-1， TLR4， and NF-κB （P<0.05 or P<0.01）. ConclusionInjecting MSU crystal resulted in local inflammatory injury of the joints in the mouse model of AGA. The treatment with Huanglian Jiedutang may alleviate the inflammatory injury by regulating the NLRP3 inflammasome and TLR4/NF-κB signaling pathway.

Application of single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical trials / 中国针灸

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.

Exploring acupuncture treatment strategies for snoring based on meridian theory / 中国针灸

Starting from the perspective of meridian theory, this article briefly analyzes the meridian pathophysiology of snoring and the relationship between snoring and meridian theory. It proposes that acupuncture treatment for snoring should focus on regulating qi from the shaoyang meridians, harmonizing the spirit by the governor vessel, resolving phlegm through the three yang meridians, and harmonizing qi and blood from the yangming meridians. Additionally, attention is placed on both the root cause and the symptoms, the theory of "four seas". The ultimate goal is to promote the flow of meridian and qi-blood, improve symptoms such as nighttime snoring, poor sleep quality, and daytime sleepiness, and achieve the desired outcome of stopping snoring and ensuring restful sleep.

Influencing factors of early activity in patients with acute ischemic stroke based on social ecological model: A qualitative study / 中南大学学报(医学版)

OBJECTIVES@#Acute ischemic stroke (AIS) is one of the main causes of disability in middle-aged and elderly people, and early activity plays an important role in functional recovery. This study aims to understand the factors that affect the implementation of early activity in patients with AIS and to provide reference for promoting early activity implementation and developing intervention strategies for AIS patients.@*METHODS@#Using purposive sampling, 19 AIS patients and their caregivers who visited at Stroke Center in the Third Xiangya Hospital of Central South University and the Third Hospital of Changsha from June to December 2021, as well as 19 medical staff, hospital administrators, or community workers providing medical health services to stroke patients, were selected as interviewes. A semi-structured interview was conducted based on the social ecological theory model, and the Colaizzi seven-step method was used to analyze the interview data.@*RESULTS@#According to qualitative interview results, the factors affecting early activity in AIS patients were summarized into 4 themes and 12 sub-themes: medical staff factors (insufficient knowledge and skills, insufficient knowledge of early activity, unclear division of responsibilities), patient factors (severity of the disease, lack of knowledge, psychological pressure, fear of falling), social environmental factors (lack of social support, shortage of human resources and rehabilitation equipment, insufficient medical insurance support), and evidence and norms (the evidence for early activity needs improvement, lack of standardized early activity procedures).@*CONCLUSIONS@#Early activity in AIS patients is impacted by factors at multiple levels, including medical staff, patients, social environment, and evidence and norms. Developing comprehensive intervention strategies to address these factors can promote early activity implementation in AIS patients.

An anterolateral thigh perforator chimeric flap combined with calcium sulfate impregnated with vancomycin for treatment of chronic fracture-related infection complicated with extensive soft-tissue defects / 中华创伤骨科杂志

Objective:To investigate the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate in the treatment of chronic infection after internal fixation of calf fracture with soft tissue defects.Methods:Retrospectively analyzed were the data of 16 patients with chronic infection combined with extensive soft tissue defects after internal fixation of calf fracture who had been admitted to Department of Orthopedics, Shenzhen Hospital Affiliated to Peking University from September 2008 to November 2020. There were 11 males and 5 females, aged from 16 to 62 years (average, 37 years). Infection sites: the upper tibia in 4 cases, the middle and lower tibia in 10 cases, and the middle fibula in 2 cases. According to the Cierny-Mader classification, all patients were anatomical type III and by the host classification, there were 14 cases of type B and 2 cases of type C type. The areas of soft tissue defects ranged from 6 cm × 4 cm to 23 cm × 14 cm. All patients were treated by transplantation of an anterolateral thigh chimeric perforator flap combined with vancomycin-loaded calcium sulfate therapy. At the last follow-up, the curative efficacy was evaluated according to the Paley fracture union scoring.Results:All patients were followed up for 8 to 24 months (mean, 16 months). Complete flap survival was achieved in 15 flaps and partial survival in one. According to the Paley fracture union scoring at the last follow-up, the curative efficacy was evaluated as excellent in 15 cases and as good in one. Both the grafted artificial bone and the tibia and fibula achieved bone union after 6 to 12 months (mean, 8.9 months). Infection with chronic sinus tract pus recurred in one case at post-operative one year. After re-debridement, the infection was controlled and the wound healed. The plate internal fixation was replaced by the unilateral or annular external fixator in 14 patients and retained in 2 patients. The lengths of the bone defects averaged 2.4 cm and the time for the external fixation 10.5 months (from 8 to 14 months).Conclusion:In the treatment of chronic infection after internal fixation of calf fracture with extensive soft tissue defects, the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate is satisfactory, because the flap can fully cover the bone and soft tissue defects while the vancomycin-loaded calcium sulfate can effectively control the infection.

Huanglian Jiedutang Regulates Inflammatory Immunity to Relieve Rheumatoid Arthritis / 中国实验方剂学杂志

ObjectiveTo observe the effects of Huanglian Jiedutang on pathological and immune damage in collagen-induced arthritis （CIA） model mice， and to explore the possible mechanism of Huanglian Jiedutang in relieving rheumatoid arthritis. MethodTwenty-four DBA/1 mice were randomly divided into normal group， model group， methotrexate group and Huanglian Jiedutang group， with six mice in each group. The CIA mice model were established using type Ⅱ collagen induction. The administration groups were respectively treated with Huanglian Jiedutang （5 g·kg-1） and methotrexate （0.5 mg·kg-1）. The joint swelling symptoms of the mice were observed， and the arthritis index was scored every 3 days. Flow cytometry was employed to detect granulocytes， monocytes， and T lymphocytes in peripheral blood. The expression of inflammatory cytokines in joint was determined by real-time polymerase chain reaction （Real-time PCR）. The ankle joint was scanned by micro-computed tomography （Micro-CT）， and the histopathological changes were observed through hematoxylin-eosin （HE） staining. ResultCompared with the normal group， the modeling led to joint swelling， elevated the joint index score （P<0.05）， increased the proportion of granulocytes （P<0.05） and decreased that of monocytes and T lymphocytes （P<0.01） in peripheral blood， and raised the neutrophil-to-lymphocyte ratio （NLR） （P<0.01）. Further， it up-regulated the expression of inflammatory cytokines such as tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 in joint （P<0.01）. Micro-CT showed obvious bone destruction in the ankle joint， and pathological examination revealed the infiltration of a large number of inflammatory cells and the synovial hyperplasia of joint tissue. Compared with the model group， Huanglian Jiedutang alleviated the symptoms of joint swelling， lowered the score of arthritis index （P<0.05）， increased the proportion of T lymphocytes and lowered NLR （P<0.01）. Moreover， it down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in joint （P<0.01） and alleviated the bone destruction and pathological injury of joint tissue. ConclusionType Ⅱ collagen caused systemic and local inflammatory immune damage in CIA mice. Huanglian Jiedutang alleviates such injury， especially for that in local joint， thereby inhibiting joint injury and bone destruction in CIA mice.

Ginkgo diterpene lactone improves depression-like behaviors and affects cytokine and neurotransmitter levels in a rat model of chronic unpredictable mild stress / 中华微生物学和免疫学杂志

Objective:To investigate the effects of Ginkgo diterpene lactone on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS) and its mechanism.Methods:Forty SD rats were randomly divided into five groups, which were control group, CUMS group, CUMS+ low-dose Ginkgo diterpene lactone group (1.5 mg·kg -1·d -1), CUMS+ medium-dose Ginkgo diterpene lactone group (3 mg·kg -1·d -1) and CUMS+ high-dose Ginkgo diterpene lactone group (6 mg·kg -1·d -1). CUMS rat model was established by continuous stress for six weeks, and the rats were given corresponding treatment in the last three weeks. Sucrose preference test was performed during the stress and drug administration, and behavior tests were performed after the stress and drug administration. After behavior tests, hippocampus, hypothalamus and serum samples were collected to detect inflammatory factors and neurotransmitter. Results:Chronic stress caused depression-like behaviors in rats, while continuous treatment with Ginkgo diterpene lactone could effectively improve sucrose preference, forced swimming immobility time and open field test scores in CUMS rats. It was found that Ginkgo diterpene lactone could significantly improve the decreased secretion of IL-1β and IFN-γ in plasma, and significantly increase the secretion of IL-10 and IL-4 caused by CUMS. In addition, CUMS caused hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis in rats, which manifested as increased secretion of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (COR). The negative feedback of HPA hypermodulated the release of neurotransmitters in the hippocampus, causing the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) in the brain of CUMS rats to decrease. However, Ginkgo diterpene lactone could significantly inhibit HPA axis hyperfunction and increase neurotransmitter levels in the brain.Conclusions:Ginkgo diterpene lactone can effectively improve the depression-like behaviors of CUMS rats through regulating the immune environment, inhibiting the HPA axis hyperfunction and increasing neurotransmitter release.

Identification of small molecule sirtuin-1 inhibitors for treating acute myeloid leukemia based on molecular docking, quantitative structure-activity relationships and molecular dynamics / 药学学报

The purpose of this study was to discover novel inhibitors of sirtuin-1 (SIRT1) that could be used in the treatment of acute myeloid leukemia (AML). Eight potential SIRT1 inhibitors were identified from 231 511 natural drug-like molecules by virtual screening-based molecular docking and molecular mechanics-generalized Born surface area (MM-GBSA) calculation of binding free energies. Using existing SIRT1 inhibitor molecules as training and test sets, a series of quantitative structure-activity relationship models were established, and the best quantitative structure-activity relationship (QSAR) model was used to predict the IC50 of these 8 potential inhibitor molecules for SIRT1. Subsequently, molecular dynamics simulations were performed to verify the binding mode and stability of these complexes of potential inhibitors and SIRT1 protein. Finally, the activity of these potential SIRT1 inhibitors was verified by cell proliferation assays of OCI-AML2, OCI-AML3 and MV4-11 cells and SIRT1 enzyme activity assays, and it was found that 5 compounds could inhibit AML cell proliferation. Among them, the most active compound, ZINC000001774455, had an IC50 of 2.29 ± 0.09 μmol·L-1 with OCI-AML2 cells, and at a concentration of 1 μmol·L-1, the inhibitory ratio of this compound on SIRT1 protein activity was 65.33%. ZINC000001774455 can be used as a lead compound for the development of new AML treatments.

Clinical effect of multicenter multidisciplinary treatment in children with renal malignant tumors / 中国当代儿科杂志

OBJECTIVE@#To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors.@*METHODS@#A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children.@*RESULTS@#Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%.@*CONCLUSIONS@#Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.