Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells / 中国结合医学杂志

OBJECTIVE@#To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification.@*METHODS@#Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway.@*RESULTS@#The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway.@*CONCLUSION@#Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

Lumbar Core Muscle Stability Training Combined with Kinesiology Taping Technique in Rehabilitation Treatment of Lumbar Disc Herniation / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical efficacy of lumbar core muscle stability training combined with kinesiology taping technique in the rehabilitation treatment of lumbar disc herniation （LDH）. MethodsA total of 99 LDH patients treated in Ningbo Yinzhou No. 2 Hospital from January 2018 to January 2020 were selected and divided into control group （n=49） and observation group （n=50）. Kinesiology taping technique was applied to patients in the control group and patients in the observation group were treated with lumbar core muscle stability training combined with kinesiology taping technique， then we compared the therapeutic effect， lumbar function and pain degree， surface electromyography of lumbar extensor muscles， lumbar range of motion， LDH recurrence and skin allergies before and after the treatment between the two groups. ResultsAfter 4 weeks of treatment， compared with those in the control group， in the observation group， the visual analogue scale （VAS） and Oswestry disability index （ODI） scores were significantly lower （P<0.05）； the Japanese Orthopaedic Association （JOA） score， mean power frequency of lumbar extensor muscles， integral electromyography value and lumbar function score were significantly higher （P<0.05）. During the treatment， there was no significant difference in the incidence of complications between two groups （P>0.05）. After 4 weeks of treatment， the observation group had a significantly lower LDH recurrence rate than the control group （P<0.05）. ConclusionLumbar core muscle stability training combined with kinesiology taping technique achieves a significantly better therapeutic effect than kinesiology taping technique in the rehabilitation treatment of LDH and can effectively relieve muscle fatigue， help alleviate lumbar spine pain and improve the function of lumbar spine.

Recent progress on the effects of structured lipids and fluidity of plasma membrane on tumor metastasis / 药学学报

The lipid composition of cell plasma membranes of aggressive tumors is significantly altered from normal, affecting the membrane fluidity and function. Plasma membrane fluidity involves multiple steps in tumor invasion and metastasis, including cell movement, adhesion, lateral diffusion of membrane molecules, signal transduction, material exchange and so on. This review highlights the difference in plasma membrane lipid composition and fluidity between normal and cancer cells, as well as the correlation with the invasion and metastasis potential of cancer. We also point out that the proliferation, invasion and metastasis of tumors can be inhibited by improving membrane fluidity or interfering with the membrane structured lipid composition, this focusing more on changing the biophysical properties of cancer cell membranes, and providing a novel strategy that works for treatment of tumor metastasis.

Effects of osthole on renal oxidative stress injury in aged spontaneously hypertensive rats by regulating PI3K/Akt/mTOR signaling pathway / 中国临床药理学与治疗学

AIM: To explore the mechanism of osthole on elderly spontaneously hypertensive rats. METHODS: 20-month-old spontaneously hypertensive rats (SHRs) and healthy Wistar-Kyoto (WKY) rats were purchased. SHRs were treated with osthole (i.g.) for 8 weeks. The systolic blood pressure and diastolic blood pressure of rats were monitored. Hematoxylin-eosin staining (H&E), periodic acid-schiff staining (PAS) and Masson staining were used to observe the pathological changes of rat kidney tissues. The activity of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) in rat kidney was detected by ELISA kit. PI3K/Akt/mTOR signaling pathway related proteins were detected by western blot. RESULTS: Osthole reduced the systolic and diastolic blood pressure of SHRs, improved the histopathological changes of SHRs kidney, reduced the activity of MDA in SHRs kidney, and increased the activity of SOD and GSH. Osthole reduced the levels of p-PI3K, p-Akt and p-mTOR. CONCLUSION: Osthole reduces the activity of PI3K/Akt/mTOR signaling pathway and exerts a protective effect on renal oxidative stress injury in aged spontaneously hypertensive rats.

Effect of Early Intervention of Yishen Huazhuo Prescription on Learning and Memory of Accelerated Aging SAMP8 Mice and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo investigate the impact of early intervention with Yishen Huazhuo prescription （YHP） on the learning and memory of accelerated aging model mice， as well as its underlying mechanism. MethodForty-eight 3-month-old male SAMP8 mice were randomly assigned into four groups， including the model group， low-dose YHP group， high-dose YHP group， and donepezil group. Additionally， 24 SAMR1 mice of the same age were divided into a control group and a YHP treatment control group， each consisting of 12 mice. The YHP groups received YHP at doses of 6.24 g·kg-1 and 12.48 g·kg-1， while the donepezil group was treated with donepezil at a dose of 0.65 mg·kg-1. The model group and control groups were given physiological saline. The mice were gavaged once daily for a duration of four weeks. Spatial learning and memory abilities of mice were assessed using the Morris water maze test. Immunofluorescence staining was employed to evaluate neuronal density as well as expression levels of M1 microglial （MG） polarization marker inducible nitric oxide synthase （iNOS） and M2 MG polarization marker arginase-1 （Arg-1） in the hippocampus region. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of pro-inflammatory factor interleukin 1β （IL-1β） and anti-inflammatory factor transforming growth factor-β1 （TGF-β1）. Furthermore， Western blot analysis was conducted to determine expressions of amyloid β peptide1-42 （Aβ1-42） along with triggering receptor expressed on myeloid cells 2 （TREM2）/nuclear factor kappa B （NF-κB） signaling pathway-related proteins TREM2， phospho （p）-NF-κB p65， and phospho-inhibitory kappa B kinase β （IKKβ） in the hippocampus. ResultCompared with the control group， the model group exhibited a significantly prolonged escape latency （P<0.01）， a significant reduction in neuron-specific nuclear protein （NeuN） expression in the hippocampus， a significant increase in iNOS expression in MG， and a significant decrease in Arg-1 expression. The serum IL-1β content was significantly increased， while the TGF-β1 content was significantly decreased. Additionally， there was a significant decrease in TREM2 expression in the hippocampus and significant increases in p-NF-κB p65， p-IKKβ， and Aβ1-42 expressions （P<0.05， P<0.01）. However， no significant changes were observed in escape latency， times of crossing the platform， and hippocampal NeuN expression in the YHP treatment control group. Conversely， iNOS expression in MG as well as the hippocampal p-NF-κB p65， p-IKKβ， and Aβ1-42 expressions were significantly decreased. Furthermore， TREM2 expression was significantly increased （P<0.05， P<0.01）. In comparison to the model group， the low-dose YHP group showed a significantly shortened escape latency and an increased number of crossing the platform （P<0.05， P<0.01）. In the high-dose YHP group， the escape latency was significantly shortened （P<0.05）. In the low-dose YHP group， high-dose YHP group， the expression of NeuN in the hippocampus was significantly increased， the expression of iNOS in MG was significantly decreased， and the expression of Arg-l was significantly increased. The serum IL-1β content was significantly decreased， while the TGF-β1 content was significantly increased. Furthermore， the expression of TREM2 in the hippocampus was significantly increased， and the expressions of p-NF-κB p65， p-IKKβ， and Aβ1-42 were significantly decreased （P<0.01）. ConclusionEarly YHP intervention may promote the transformation of hippocampal MG from M1 to M2 by regulating the TREM2/NF-κB signaling pathway， reduce the release of neuroinflammatory factors， protect hippocampal neurons， and reduce the deposition of Aβ1-42， and finally delay the occurrence of learning and memory decline in SAMP8 mice.

Imaging study on thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis / 中国骨伤

OBJECTIVE@#To observe the alteration of thoracic and lumbar physiological curvature in adolescent idiopathic scoliosis(AIS) and the difference of physiological curvature between different types of scoliosis.@*METHODS@#A retrospective analysis was conducted on 305 adolescent patients taken full spine X-ray in our hospital from January 2017 to December 2021. The patients were divided into normal group and scoliosis group. The normal group was composed of 179 patients, 79 males and 100 females, aged 10 to 18 years old with an average of (12.84±2.10) years old, with cobb agle less than 10 degrees. The scoliosis group was composed of 126 patients, 33 males and 93 females, aged 10 to 18 years old with an average of (13.92±2.20) years old. The gender, age, Risser sign, thoracic kyphosis(TK) and lumbar lordosis(LL) in 2 groups were compared, and the TK and LL were also compared between different genders, different degrees of scoliosis and different segments of scoliosis.@*RESULTS@#The female ratio(P=0.001) and age (P<0.001) in scoliosis group were higher than them in normal group; the ratio of low-grade ossification was higher in normal group than in scoliosis group(P=0.038). TK was significantly smaller in scoliosis group than in normal group(P<0.001), but there was no significant difference in LL between the 2 groups(P=0.147). There were no significant difference in TK and LL between male and female. The TK was significantly bigger in mild AIS patients than in moderate AIS patients(P<0.05), but there was no significant difference in LL between mild and moderate patients(P>0.05). The TK and LL in different segments scoliosis were not found significant difference.@*CONCLUSION@#The physiological curvature of thoracic and lumbar spine is independent of gender. The thoracic physiological curvature becomes smaller in AIS patients, but lumbar curvature remains unchanged. The thoracic physiological curvature in mild AIS patients is greater than that in moderate AIS patients, but the lumbar curvature is almost unchanged between mild and moderate scoliosis and is similar with that in normal adolescent. The alteration of thoracic and lumbar physiological curvature in AIS patients may be related to relative anterior spinal overgrowth, and the specific detailed mechanism needs to be further studied.

Progress of researches on Blastocystis hominis infection among patients with inflammatory bowel disease and irritable bowel syndrome / 中国血吸虫病防治杂志

Blastocystis is a common unicellular intestinal protozoa in humans and animals, and the most common clinical manifestations of infections include abdominal pain and diarrhea. Based on the sequence of the small-subunit ribosomal RNA (SSU rRNA) gene, 28 subtypes of B. hominis (ST1 to ST17, ST21 and ST23 to ST32) have been characterized. Previous studies have demonstrated that B. hominis infection is strongly associated with inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other intestinal diseases, which threatens the health and quality of life among patients with B. hominis infection and is considered as an important public health problem. This review summarizes the progress of researches on B. hominis infection among IBD and IBS patients during the past 20 years, so as to provide insights into management of blastocystosis in China.

The posture decoding technique can improve the pelvis carriage and lumbar motion of patients with lower crossed syndrome, relieving back pain and relaxing the back muscles / 中华物理医学与康复杂志

Objective:To observe the clinical effectiveness of manual therapy based on posture decoding for patients with lower crossed syndrome (LCS).Methods:Thirty-six LCS patients were randomly divided into an observation group and a control group, each of 18. The observation group received manual therapy based on posture decoding, while the control group was treated with proprioceptive neuromuscular facilitation (PNF), both in 20min sessions, once a week for 4 weeks. Before the experiment, after one, two and four weeks of treatment and followed-up 4 and 8 weeks later, both groups were evaluated using a visual analogue scale (VAS), the Oswestry Disability Index (ODI) and finger-floor distance (FFD). Anterior pelvic tilt angles (ASIS-PSISs), sacral slopes (SS), lumbar curve index (LCI) and surface EMG flexion-relaxation ratios (FRRs) were also recorded from both groups before and after the treatment.Results:After one and four weeks of the treatment, the average VAS, ODI, and FFD had decreased significantly in both groups, with all significantly lower in the observation group, on average. At the final follow-up, the average VAS and ODI scores of both groups were significantly lower than before the treatment, with those of the observation group significantly lower than the control group′s averages. After 4 weeks of treatment significant differences were observed also in the group′s average ASIS-PSISs, SSs and LCIs compared with before the treatment. And right after the treatment the left and right surface electromyography FRRs of the observation group were significantly higher than those of the control group.Conclusion:Manual therapy based on posture decoding can significantly improve the pelvis forward angle and lumbar motion of LCS patients, relieving back pain and relaxing back muscles.

Ultrashortwave therapy can inhibit inflammation and promote recovery from spinal cord injury / 中华物理医学与康复杂志

Objective:To observe any effect of ultrashortwave (USW) therapy on inflammatory cytokines and the MAPK pathway of rats with a spinal cord injury.Methods:Seventy-nine Sprague-Dawley rats were randomly divided into a control group ( n=35), an intervention group ( n=35) and a sham group ( n=9). Allen′s method was used to establish a contusion model of SCI in the rats of the control and intervention groups, while the sham group′s spinal tissues were exposed but not stricken. Beginning twenty-four hours after SCI modeling, the intervention group was given 7min of USW therapy daily, five days a week till the day of sacrifice for sampling the target area of spinal cord for tests. Then, motion function was evaluated using Basso, Beattie and Bresnahan (BBB) scoring. One, three and seven days after the SCI modeling, immunofluorescence and western blotting were employed to observe any changes in inflammatory factors and the MAPK pathway in the lesioned area. Results:Fourteen days after the modeling the average BBB score of the intervention group was significantly higher than the control group′s average. Moreover, 7 days after the modeling the average content of the domains containing protein 3 (NLRP3), interleukin-6 (IL-6), IL-6 receptor and tumor necrosis factor-α (TNF-α) in the target area of the spinal cord of sham group showed significantly lower levels than in the other 2 groups. And the levels in the intervention group were significantly lower than in the control group. Seven days after the modeling the number of cells positive for zinc finger protein 36 (TTP) in the lesioned area of the intervention group was significantly greater than among the control group. At the same time the levels of MAPK-activated protein kinase 2 (MK2), phosphorylated-mitogen-activated protein kinase-activated version (p-MK2) and TTP in the control and intervention groups were significantly higher than in the sham group. And there were significant differences between the intervention group and control group in the levels of MK2, p-MK2 and TTP.Conclusion:Ultrashortwave therapy can inhibit inflammation by regulating the MAPK inflammatory pathway, promoting the recovery of motion functions, at least in rats.

Predictive model of fecal or urinary incontinence among older adults in China / 中华老年医学杂志

Objective:To construct and validate a predictive model of fecal/urinary incontinence among older adults in China.Methods:Data was obtained from the Seventh Chinese Longitudinal Healthy Longevity Survey in 2018.In the questionnaire, "Are you able to control your bowel and urine" , was regarded as the main effect indicator.Receiver operating curves(ROC)were used to find the best cut-off values of calf circumference for predicting fecal/urinary incontinence, and univariate Logistic model method was used to explore the potential factors associated with fecal/urinary incontinence among community-living older adults in China.A random sampling method was used to extract 70% of the survey data as the training set, and the remaining 30% of the survey data as the test set.A multivariate Logistic regression analysis was conducted in the training set to build a prediction model that encompassed all predictors, and a nomogram was plotted.Results:Logistic regression analysis showed that age, small calf circumference(male <28.5 cm, female <26.5 cm), inability to walk 1 km continuously, inability to lift 5 kg items, inability to do three consecutive squats, limited daily activities, and a history of urinary system disorders, nervous system disorders, and cerebrovascular disorders were all risk factors for fecal/urinary incontinence for older adults in China.Female, better socioeconomic status, and normal body mass index were protective factors for fecal/urinary incontinence.The Logistic regression model for predicting fecal/urinary incontinence among Chinese older adults was constructed using the above twelve factors.The consistency index(C-index)value of the model was 0.907, indicating that the model had good predictive ability.The area under the ROC curve(AUC)of the overall sample, training set and test set were 0.906(95% CI: 0.896-0.917), 0.907(95 % CI: 0.894-0.921)and 0.910(95% CI: 0.892-0.928), respectively, indicating that the model had high prediction ability and good discrimination. Conclusions:Age, sex, calf circumference, ability to walk 1 km continuously, ability to lift 5 kg items, ability to do three consecutive squats, daily activities, history of urinary system disorders, nervous system disorders and cerebrovascular disorders, socioeconomic status, and body mass index were independent predictors for fecal/urinary incontinence among older adults in China.The nomogram based on the above indicators has a good predictive effect on fecal/urinary incontinence for older adults.

The mechanisms underlying metronomic chemotherapy and its application in advanced non-small cell lung cancer / 中华老年医学杂志

The morbidity and mortality of non-small cell lung cancer(NSCLC)are among the highest of all malignancies.The mechanisms concerning metronomic chemotherapy include anti-angiogenesis, immune microenvironment regulation, and cytotoxic effects, among others.As an alternative to traditional chemotherapy, metronomic chemotherapy has shown promising outcomes in the treatment of advanced NSCLC.Several clinical trials have explored the application of metronomic chemotherapy in the treatment of advanced NSCLC, either as a monotherapy or in combination with chemotherapy, anti-angiogenic therapy, targeted therapy or immunotherapy.This paper mainly reviews the mechanisms underlying metronomic chemotherapy and its clinical application in advanced NSCLC, in order to provide more evidence for the optimization of NSCLC treatment regimens.

The predictive value of the epithelial cell proliferation pathway genes for the prognosis of elderly non-small cell lung cancer patients receiving immunotherapy / 中华老年医学杂志

Objective:To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods:A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status, patients were divided into an ECP pathway-related gene mutation group(ECP mutation group, n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group, n=81). The primary endpoints were overall survival(OS)and progression-free survival(PFS). Differences in survival and efficacy between the two groups were compared, and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient, and differences in survival were compared.Results:Survival outcomes were worse in the ECP(+ )group than in the ECP(-)group(mOS: 10.9 months vs.17.1 months, HR=1.84, 95% CI: 1.09-3.08, P<0.05; mPFS: 2.8 months vs.4.2 months, HR=1.58, 95% CI: 1.00-2.51, P<0.05). Of all mutations in ECP pathway-related genes, mutations in the RB1 gene had a significant prognostic effect on all patients, with the negative prognostic effect especially prominent in ECP(+ )patients.Compared with ECP(-)patients, ECP(+ )patients had a shorter mOS(6.9 months vs.12.6 months, HR=3.14, 95% CI: 1.10-8.97, P=0.024). Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months, HR=3.23, 95% CI: 1.25-8.37, P=0.011). Conclusions:Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy, and mutations located in the clonal cluster have a stronger impact on the prognosis.

A retrospective analysis of Osimertinib in treatment of elderly patients with advanced lung adenocarcinoma with epidermal growth factor receptor mutation / 中华老年医学杂志

Objective:To evaluate the efficacy and safety of Osimertinib in the second-line and above treatment of elderly patients with advanced lung adenocarcinoma with epidermal grouth factor receptor(EGFR)mutation.Methods:A retrospective analysis of 51 elderly patients with advanced lung adenocarcinoma aged 65 years and over was performed.EGFR gene mutations were detected at baseline.The patients were treated with Osimertinib as second or later-line treatment after disease progression on prior epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)therapy.Results:The median age of the patients was 72 years old, and the median progression-free survival(PFS)with Osimertinib was 13 months(95% CI: 10.8-15.2 months). Patients with exon 19 deletion(19del)treated with Osimertinib had longer PFS than patients with EGFR 21 exon L858R mutation(12 vs.24 month, P=0.028). In patients with EGFR resistance mutation T790M(T790M-positive), the PFS of patients with 19del combined with T790M(19del / T790M-positive)was better than that of patients with L858R combined with T790M(L858R / T790M-positive)(10 vs.28 months, P=0.029). After Osimertinib treatment, 43.8% of patients had brain or meningeal progression.The most commonly used agents for treatment after resistance to Osimertinib are antiangiogenic drugs.The common adverse reactions of Osimertinib were diarrhea(31.4 %), followed by dry skin with itching(29.4%)and rash(25.5 %). Most adverse reactions were grade 1 to 2, and one patient discontinued the drug intermittently due to grade 3 hematological adverse reactions. Conclusions:Osimertinib is effective and well tolerated in elderly patients with advanced EGFR-mutant lung adenocarcinoma.

Research progress of measurement tools for health-related quality of life in patients with spinal metastases / 中华骨科杂志

The Health-Related Quality of Life (HRQoL) pertains to patients' subjective contentment concerning their physical, psychological, and social well-being throughout disease treatments. Predominantly employed HRQoL metrics in spinal metastases comprise the 36-item Short-Form Health Survey (SF-36), EuroQoL Five Dimensions Questionnaire (EQ-5D), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and the Functional Assessment of Cancer Therapy-General (FACT-G). In clinical applications, due to their broad application and diverse disease types, combined with the lack of specificity in the scale content and the prolixity of their questionnaires, these tools often fail to capture the nuanced experiences of patients, thereby compromising the reliability and validity of the results. The Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ), developed by the Spine Oncology Study Group, offers a tailored metric for spinal metastases, encapsulating both specificity and inclusivity. Its proven robust reliability and validity make it invaluable for decision-making and therapeutic efficacy appraisals. The Patient-Reported Outcome Measurement Information System (PROMIS), a novel metric suitable across many medical disciplines, facilitates cross-sector data acquisition, substantially augmenting the precision, sensitivity, and credibilityof assessments, and is pivotal in clinical investigations and interventions. As it continually evolves, PROMIS consistently outperforms traditional metrics in evaluative capacities, exhibiting impressive and consistent proficiency in prognostications, preoperative assessments, and therapeutic outcome evaluations within the spinal metastasis domain. Presently, Chinese research on the HRQoL of spinal metastasis patients remains scant, and choosing an apt, precise, and dependable metric holds significant clinical relevance. Drawing upon extant scholarly publications, this review concluded the current global HRQoL tools for spinal metastases, aiming to furnish insights for the clinical management and research pertaining to spinal metastases.

Value of quantitative parameters of enhanced MRI in predicting collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus / 中华放射学杂志

Objective:To explore the value of quantitative parameters of enhanced MRI in predicting the establishment of inferior vena cava collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus.Methods:Sixty-seven patients with renal cell carcinoma and inferior vena cava tumor thrombus who underwent radical resection and inferior vena cava venography in First Medical Center, PLA General Hospital from May 2006 to January 2021 were included retrospectively. According to the results of inferior vena cava venography, the patients were divided into two groups: the well-established collateral circulation group ( n=41) and the poor-established collateral circulation group ( n=26). Quantitative parameters were measured on preoperative enhanced MRI images, including tumor size, the maximum diameter of bilateral lumbar veins, the length of tumor thrombus, and the long and short diameters of tumor thrombus. Student′s t test or Mann-Whitney U test was used for comparison between the two groups. The independent risk factors related to the establishment of collateral circulation were obtained by binary logistic regression analysis and the model was established. The receiver operating characteristic curve was employed to evaluate MRI quantitative parameters and the logistic model, and the area under the curve (AUC) was compared by the DeLong test. Results:Between the well-established collateral circulation group and the poor-established collateral circulation group, the maximum diameter of the right lumbar vein, the maximum diameter of the left lumbar vein, the length of the tumor thrombus, the long diameter of the tumor thrombus, and the short diameter of the tumor thrombus were different significantly ( P<0.05). There was no significant difference in the tumor size between the two groups ( t=0.30, P=0.766). The AUC of the maximum diameters of the right lumbar veins and left lumbar veins, length of tumor thrombus, long and short diameters of tumor thrombus in predicting the collateral circulation were 0.917 (95%CI 0.824-0.971), 0.869 (95%CI 0.764-0.939), 0.756 (95%CI 0.636-0.853), 0.886 (95%CI 0.785-0.951), and 0.906 (95%CI 0.809-0.963). The AUC of the maximum diameter of the right lumbar vein and the short diameter of the tumor thrombus were larger than those of the length of the tumor thrombus, and the differences were statistically significant ( Z=2.25, 2.04, P=0.025, 0.041), but the AUC between other parameters had no significant difference ( P>0.05). The maximum diameter of the right lumbar vein (OR 24.210, 95%CI 2.845-205.998), the maximum diameter of the left lumbar vein (OR 20.973, 95%CI 2.359-186.490), and the length of the tumor thrombus (OR 23.006, 95%CI 2.952-179.309) were independent risk factors for predicting the establishment of inferior vena cava collateral circulation. The AUC of logistic model was 0.969 (95%CI 0.931-1.000). Conclusion:Quantitative parameters of tumor thrombus and lumbar vein based on enhanced MRI have a good ability in predicting the establishment of inferior vena cava collateral circulation in patients with renal cell carcinoma and inferior vena cava tumor thrombus. The maximum diameter of bilateral lumbar veins and the length of the tumor thrombus were independent risk factors for inferior vena cava collateral circulation.

The value of deep learning technology based on mammography in differentiating breast imaging reporting and data system category 3 and 4 lesions / 中华放射学杂志

Objective:To explore the value of deep learning technology based on mammography in differentiating for breast imaging reporting and data system (BI-RADS) category 3 and 4 lesions.Methods:The clinical and imaging data of 305 patients with 314 lesions assessed as BI-RADS category 3 and 4 by mammography were analyzed retrospectively in Shenzhen People′s Hospital and Shenzhen Luohu People′s Hospital from January to December 2020. All 305 patients were female, aged 21 to 83 (47±12) years. Two general radiologists (general radiologist A and general radiologist B) with 5 and 6 years of work experience and two professional breast imaging diagnostic radiologists (professional radiologist A and professional radiologist B) with 21 years of work experience and specialized breast imaging training were randomly assigned to read the imaging independently at a 1∶1 ratio, and then to read the imaging again in combination with the deep learning system. Finally, breast lesions were reclassified into BI-RADS category 3 or 4. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the diagnostic performance, and the differences of AUCs were compared by DeLong method.Results:The AUC of general radiologist A combined with deep learning system to reclassify BI-RADS category 3 and 4 breast lesions was significantly higher than that of general radiologist A alone (AUC=0.79, 0.63, Z=2.82, P=0.005, respectively). The AUC of general radiologist B combined with deep learning system to reclassify BI-RADS category 3 and 4 breast lesions was significantly higher than that of general radiologist B (AUC=0.83, 0.64, Z=3.32, P=0.001, respectively). There was no significant difference in the AUCs between professional radiologist A combined with deep learning system and professional radiologist A, and professional radiologist B combined with deep learning system and professional radiologist B in reclassifying BI-RADS category 3 and 4 breast lesions ( P>0.05). Conclusion:The deep learning system based on mammography is more effective in assisting general radiologists to differentiate between BI-RADS category 3 and 4 lesions.

The impact of image quality on the diagnostic performance of CT-derived fractional flow reserve / 中华放射学杂志

Objective:To explore the impact of coronary CT angiography (CCTA) image quality and related factors on the diagnostic performance of CT-derived fractional flow reserve (CT-FFR).Methods:Based on the CT-FFR CHINA trial, the prospective multicenter trial enrolled patients with suspected coronary artery disease who underwent CCTA, CT-FFR and FFR measurement. The subjective and objective assessments of CCTA image were performed on a per-vessel level. The objective assessments included the enhancement degree of coronary artery, the signal-to-noise ratio (SNR) of the aortic root. We used χ 2 test and DeLong test to compare the diagnostic performance of CT-FFR with FFR as the reference standard in different subjective groups (non-artifact vs. artifact), enhancement degree of coronary artery groups (≤400 vs. 401-500 vs.>500 HU), SNR of the aortic root groups (≤16.9 vs.>16.9), body mass index (BMI) groups (<25 kg/m 2 vs.≥25 kg/m 2) and heart rate groups (<75 bpm vs.≥75 bpm). FFR and CT-FFR values≤0.80 was identified as myocardial ischemia. Results:The study enrolled 317 patients with 366 vessels. All target vessels in CCTA images were successfully analyzed by CT-FFR. The accuracy, sensitivity, specificity, positive predictive value, negative predictive value and AUC of the non-artifact group were 90.45%, 86.75%, 93.10%, 90.00%, 90.76% and 0.928, respectively, and those of the artifact group were 83.23%, 87.21%, 79.01%, 81.52%, 85.33% and 0.869, respectively. The differences in accuracy and specificity were statistically significant (χ 2=4.23, P=0.040; χ 2=8.55, P=0.003). The diagnostic efficacy of CT-FFR had no statistically significant differences among different objective groups (all P>0.05). Conclusions:The artifact of CCTA image has an effect on CT-FFR in the diagnosis of myocardial ischemia. The degree of vascular enhancement, SNR, BMI, and heart rate have no significant effect on the diagnostic performance of CT-FFR.

Tetrahydroxy stilbene glycoside ameliorates neuroin-flammation for Alzheimer's disease via cGAS-STING / 中国药理学与毒理学杂志

OBJECTIVE Alzheimer's disease(AD)is the most common neurodegenerative disease worldwide.Neuroinflammation is a potential target for the patients with AD.It is attributed to activated microglia and the release of various inflammatory mediators from infec-tion,ischemia and toxin accumulation.Accumulating evi-dence has indicated that the cGAS-STING pathway driven neuroinflammation in neurological disease.TSG is a main natural active ingredient that derived from polyg-onum multiflorum.Previous research from our group found that TSG has beneficial effects of anti-aging,anti-inflammatory action and improving memory function in APP/PS1 transgenic AD mice.Here,we investigated the effects of TSG on cognitive impairment and neuroinflam-mation in APP/PS1-AD mice and explore the underly-ing mechanism by which TSG ameliorates memory func-tion in the cGAS-STING-mediated inflammatory response.METHODS The Morris water mace test and the novel object recognition test were performed to test the effects of TSG on spatial learning and cognitive and memory abil-ity in APP/PS1 double transgenic AD mice model.In addi-tion,real-time quantitative PCR,Western blotting,ELISA analysis,and flow cytometry to examine gene and pro-tein expression of cGAS-STING related pro-inflammatory cytokines and chemokines.Statistical analyses were ana-lyzed using the SPSS 25.0 package by analysis of vari-ance(ANOVA).Neuman-Keuls or Tukey's multiple-com-parisons test were conducted as ANOVA justified post hoc comparisons between group means.RESULTS We demonstrated that AD transgenic mice exhibited cognitive deficits accompanied by the elevated serum and brain inflammation.The expressions of serum inflammatory cytokines and the activation of microglia in cerebral cor-tex and hippocampus were suppressed after TSG treat-ment,which was probably attributable to the decrease of cyclic GMP-AMP synthase(cGAS)and stimulator of interferon genes(STING)triggered immune response.Additionally,the data showed that TSG treatment reduced the expression level of inflammatory cytokines(IL-1β,TNF-α,IFN-β,IFN-α)in microglial cells BV2 primed with LPS and IFN-γ.CONCLUSION TSG implicated the health benefits in preventing cognitive disorders by inhib-iting neuroinflammation via cGAS-STING signalling path-way in AD.

Cornel iridoid glycoside alleviates microglia-mediated inflammatory response via NLRP3/calpain pathway / 中国药理学与毒理学杂志

OBJECTIVE Vascular dementia(VaD)is associated with cerebral hypoperfusion,which results in long-term cognitive impairment and memory loss.Neuroin-flammation is an important mechanism of vascular demen-tia.Cornel iridoid glycoside(CIG)is the major active con-stituent isolated from the ripe fruit of Cornus officinalis.Previous studies have shown that CIG enhances neuro-logical function in VaD rats.In the present research,we attempted to clarify the molecular processes underlying the role of CIG on neuroinflammation in VaD.METHODS In vivo,we created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries(2VO).The rats were divided into sham operation,2VO,2VO + CIG(60 and120 mg·kg-1·d-1),and 2VO+ butylphthalide(100 mg·kg-1·d-1)groups and then treated rats with differ-ent concentrations of CIG.In vitro,BV2 microglia cells were induced with bacterial lipopolysaccharide(LPS)and interferon-γ(IFN-γ)to construct the model of microglias with analog neuroinflammation.Histopathology and biel-schowsky silver staining were used to detect myelin integrity and neuronal loss.Immunofluorescence was used to observe changes in microglia.Magnetic Luminex Assay was used to detect changes in inflammatory fac-tors.Western blotting,ELISA or calpain activity assay was used to measure the expression and activity of cal-pain,as well as the expression of NLRP3 inflammasome protein.Furthermore,NLRP3 overexpressing cells were used to further elucidate the potential anti-inflammatory molecular mechanism of CIG.RESULTS ① CIG improved neuronal impairment in the brain of 2VO rats.②CIG increased white matter(WM)integrity in 2VO rats.③ CIG reduced microglia inflammatory response in the cortex and hippocampus of 2VO rats.④ CIG inhibited calpain activity in the cortex and hippocampus of 2VO rats.⑤ CIG exerted anti-inflammatory effects on BV2 cells stimulated by LPS and IFN-γ.⑥ CIG Inhibited the expression and activity of calpain in LPS/IFN-γ-activated BV2 cells.⑦ The main component of CIG had a weak binding force to calpain1.⑧ CIG inhibited the activation of the NLRP3 inflammasome.⑨CIG reduced the activity of calpain induced by NLRP3 overexpression.CONCLU-SION CIG inhibits microglial polarization into a proinflam-matory state by attenuating the assembly of the NLRP3 inflammasome and calpain activation,thus reducing brain inflammation,WM injury,and the loss of neurons.To sum up,the present study suggests that CIG inhibits neuroinflammation.The NLRP3/calpain pathway may be the main pathway by which CIG protects against neuroin-flammation.

Reform and practice of blended teaching of biochemistry and molecular biology in the context of new medicine / 中华医学教育探索杂志

Objective:To investigate the application effect of the blended teaching model of "pre-class synchronous small private online course (SPOC)+ flipped classroom+post-class knowledge expansion" in the theoretical teaching of biochemistry and molecular biology. Methods:A total of 951 students majoring in clinical medicine, preventive medicine, and pharmacy in the class of 2020 in Qiqihar Medical College were selected as teaching reform research group (experimental group), and their curriculum relied on the self-built massive open online course (MOOC) curriculum and the MOOC resources of Chinese universities to construct a blended teaching model; the reform methods such as small class grouping, case-based learning, and diversified examination were adopted to carry out theoretical flipped teaching activities with cross integration of cases and knowledge points as the main line. A total of 847 students majoring in clinical medicine, preventive medicine, and pharmacy in the class of 2019 were selected as control group, and the traditional teaching method was used for theoretical courses. The courses were evaluated by offline assessment and online assessment, and feedback information was collected through examination scores, questionnaire survey, and online voting. SPSS 20.0 was used for statistical analysis, and the t-test was used for comparison between groups. Results:The experimental group had a significantly higher total score of final examination than the control group [(92.12±3.88) vs. (86.73±5.27), P<0.05]. The questionnaire survey showed that the students in the experimental group showed a relatively high degree of satisfaction with the blended teaching reform, which increased their participation, experiencing, and sharing activities. The students majoring in clinical medicine in the class of 2020 believed that they had established clinical thinking ability (263, 92.61%) and become familiar with the clinical manifestations and pathogenesis of common diseases (262, 92.25%); the students majoring in preventive medicine in the class of 2020 believed that they had increased their awareness of serving the public (151, 93.21%) and developed the ability to teach and guide healthy living (148, 91.36%); the students majoring in pharmacy in the class of 2020 believed that they had mastered the mechanism of action of drugs for disease treatment (138, 93.24%) and understood the importance of rational drug use in clinical practice (135, 91.22%). Conclusion:The blended teaching model realizes student-centered teaching, stimulates the interest and initiative in learning, and improves learning outcome, thereby improving teaching quality to a certain extent.