Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.

OBJECTIVE: Colorectal cancer (CRC), a prevalent malignancy worldwide, has prompted extensive research into anticancer drugs. Traditional Chinese medicinal materials offer promising avenues for cancer management due to their diverse pharmacological activities. This study investigated the effects of Notopterygium incisum, a traditional Chinese medicine named Qianghuo (QH), on CRC cells and the underlying mechanism. METHODS: The sulforhodamine B assay and colony formation assay were employed to assess the effect of QH extract on the proliferation of CRC cell lines HCT116 and Caco-2. Propidium iodide (PI) staining was utilized to detect cell cycle progression, and PE Annexin V staining to detect apoptosis. Western blotting was conducted to examine the levels of apoptotic proteins, including B-cell lymphoma 2-interacting mediator of cell death (BIM), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (BAX) and cleaved caspase-3, as well as BIM stability after treatment with the protein synthesis inhibitor cycloheximide. The expression of BAX was suppressed using lentivirus-mediated shRNA to validate the involvement of the BIM/BAX axis in QH-induced apoptosis. The in vivo effects of QH extract on tumor growth were observed using a xenograft model. Lastly, APCMin+ mice were used to study the effects of QH extract on primary intestinal tumors. RESULTS: QH extract exhibited significant in vitro anti-CRC activities evidenced by the inhibition of cell proliferation, perturbation of cell cycle progression, and induction of apoptosis. Mechanistically, QH extract significantly increased the stability of BIM proteins, which undergo rapid degradation under unstressed conditions. Knockdown of BAX, the downstream effector of BIM, significantly rescued QH-induced apoptosis. Furthermore, the in vitro effect of QH extract was recapitulated in vivo. QH extract significantly inhibited the tumor growth of HCT116 xenografts in nude mice and decreased the number of intestinal polyps in the APCMin+ mice. CONCLUSION: QH extract promotes the apoptosis of CRC cells by preventing the degradation of BIM.

Effect of acupuncture and moxibustion on artery elasticity for early carotid atherosclerosis. / é’ˆç¸å¯¹é¢ˆåŠ¨è„‰ç²¥æ ·ç¡¬åŒ–æ—©æœŸæ‚£è€ è¡€ç®¡å¼¹æ€§çš„å½±å“.

OBJECTIVES: To observe the effect of acupuncture and moxibustion on arterial elasticity in patients with early carotid atherosclerosis. METHODS: A total of 62 patients with early carotid atherosclerosis were randomly divided into a blank group (12 cases, 1 cases dropped-off), a sham-acupuncture group (25 cases, 5 cases dropped-off) and an acupuncture group (25 cases, 3 cases dropped-off). Patients in the acupuncture group received acupuncture treatment, including ①acupuncture：Baihui (GV20), Yintang (GV24+), Renying (ST9), Neiguan (PC6), Yanglingquan (GB34)；②moxibustion：Yinqiguiyuan (Zhongwan ［CV12］, Xiawan ［CV10］, Qihai ［CV6］, Guanyuan ［CV4］), Sihua (Geshu ［BL17］, Danshu ［BL19］)；③Intradermal needle：Xinshu (BL15), Danshu (BL19). Patients in the sham acupuncture group received placebo acupuncture, moxibustion, an intradermal needle, and the acupoints were the same as the acupuncture group. The above treatments were performed twice a week for 12 weeks. No intervention was given to the patients in the blank group. Diet and lifestyle education was given to the three groups. The ultrafast pulse wave velocity, including beginning-systolic pulse wave velocity (BS) and end-systolic pulse wave velocity (ES), was observed before treatment and 1, 2, 3 months after treatment in the three groups. The blood lipid level and platelet count (PLT) at each time point were observed. The safety of the treatments was also evaluated. RESULTS: Compared with those before treatment, the BS and ES values of both sides in the acupuncture group decreased at 2 and 3 months after treatment (P<0.05). Compared with the blank group, the bilateral ES of the acupuncture group were decreased at 2 months after treatment (P<0.05), and the bilateral BS and ES were decreased at 3 months (P<0.05). Compared with the sham-acupuncture group, the acupuncture group showed a decrease in left BS and left ES after 3 months of treatment (P<0.05), and the overall decrease on the left side of the acupuncture group was better than that on the right side. There were no significant differences between three groups in the levels of blood lipid and PLT at each time point. No serious adverse safety events occurred in the three groups during the treatment. CONCLUSIONS: Acupuncture and moxibustion therapy can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective.

Subregions of the fusiform gyrus are differentially involved in the attentional mechanism supporting visual mental imagery in depression.

BACKGROUND: Impaired visual mental imagery is an important symptom of depression and has gradually become an intervention target for cognitive behavioral therapy. METHODS: Our study involved a total of 25 healthy controls (HC) and 23 individuals with moderate depressive symptoms (MD). This study explored the attentional mechanism supporting visual mental imagery impairments in depression using the Vividness of Visual Imagery Questionnaire (VVIQ), attentional network test (ANT), and resting-state functional magnetic resonance imaging (rs-fMRI). The intrinsic activity of attention-related regions relative to those supporting visual mental imagery was identified in depression patients. In addition, a meta-analysis was used to describe the cognitive function related to this intrinsic activity. RESULTS: The global correlation (GCOR) of the right anterior fusiform gyrus (FG) was decreased in depression patients. Attention-related areas were concentrated in the right posterior FG; the anterior and posterior functional connectivity (FC) of the FG was decreased in depression patients. Graph theoretic analysis showed that the degree of the right anterior FG was decreased, the degree of the anterior insula was increased, and the negative connection between these two regions was strengthened in depression patients. In addition, the degree of the right anterior FG, the FC between the subregions of the right FG, and the FC between the right anterior FG and insula were correlated with VVIQ scores; however, this correlation was not significant in depression patients. The meta-analysis suggested that the changes in the anterior FG in depressed patients may stem from difficulties of semantic memory retrieval. CONCLUSION: The changed intrinsic activity of subregions of the FG relative to the semantic memory retrieval may be associated with visual mental imagery impairments in depression.

Perceived stress and brain connectivity in subthreshold depression: Insights from eyes-closed and eyes-open states.

Perceived stress is an acknowledged risk factor for subthreshold depression (StD), and fluctuations in perceived stress are thought to disrupt the harmony of brain networks essential for emotional and cognitive functioning. This study aimed to elucidate the relationship between eye-open (EO) and eye-closed (EC) states, perceived stress, and StD. We recruited 27 individuals with StD and 33 healthy controls, collecting resting state fMRI data under both EC and EO conditions. We combined intrinsic connectivity and seed-based functional connectivity analyses to construct the functional network and explore differences between EC and EO conditions. Graph theory analysis revealed weakened connectivity strength in the right superior frontal gyrus (SFG) and right median cingulate and paracingulate gyrus (MCC) among participants with StD, suggesting an important role for these regions in the stress-related emotions dysregulation. Notably, altered SFG connectivity was observed to significantly relate to perceived stress levels in StD, and the SFG connection emerges as a neural mediator potentially influencing the relationship between perceived stress and StD. These findings highlight the role of SFG and MCC in perceived stress and suggest that understanding EC and EO states in relation to these regions is important in the neurobiological framework of StD. This may offer valuable perspectives for early prevention and intervention strategies in mental health disorders.

Combination of MAR and intron increase transgene expression of episomal vectors in CHO cells.

Previous work has shown that the EF-1α promoter of episomal vectors maintains high-level transgene expression in stably transfected Chinese hamster ovary (CHO) cells. However, the transgene expression levels need to be further increased. Here, we first incorporated matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE), stabilizing anti repressor elements 40 (STAR 40) elements into episomal vector at different sites and orientations, and systemically assessed their effects on transgene expression in transfected CHO-K1 cells. Results showed that enhanced green fluorescent protein (eGFP) expression levels increased remarkably when MAR X-29 was inserted upstream of the promoter, followed by the insertion of MAR1 downstream of the poly A, and the orientation had no significant effect. Moreover, MAR X-29 combined with human cytomegalovirus intron (hCMVI) yielded the highest transgene expression levels (4.52-fold). Transgene expression levels were not exclusively dependent on transgene copy numbers and were not related to the mRNA expression level. In addition, vector with MAR X-29+hCMVI can induce herpes simplex virus thymidine kinase (HSV-TK) protein expression, and the HSV-TK protein showed a cell-killing effect and an obvious bystander effect on HCT116 cells. In conclusion, the combination of MAR X-29 and hCMV intron can achieve high efficiency transgene expression mediated by episomal vectors in CHO-K1 cells.

Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme.

INTRODUCTION: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. Results：The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

Thresholds for triggering the propagation of meteorological drought to hydrological drought in water-limited regions of China.

Propagation thresholds that trigger a transition between meteorological drought and hydrological drought are poorly understood, which hinders effective establishment of drought warning systems and prevention measures. Here, propagation thresholds were assessed by firstly identifying drought events during 1961-2016 in the Yellow River Basin, China, subsequently pooling, excluding, and matching them, and finally assessing their threshold conditions by using a combined Copula function and transition rate (Tr) analysis. These results show that response time changed according to variations in drought duration and watershed characteristics. Importantly, response times increased according to the timescales over which they were studied; for example, the Wenjiachuan watershed recorded response times of 8, 10, 10, and 13 months when examined at 1-, 3-, 6-, and 12-month timescales, respectively. Additionally, the severity and duration of meteorological and hydrological drought events both increased when events were combined rather than studied individually. These effects were also amplified for matched meteorological and hydrological droughts by factors of 1.67 (severity) and 1.45 (duration), respectively. Shorter response times were identified in the Linjiacun (LJC) and Zhangjiashan (ZJS) watersheds, and correlated with their relatively small Tr values of 43 % and 47 %, respectively. Higher propagation thresholds for drought characteristics (e.g., 1.81 and 1.95 for drought severity in the LJC and ZJS watersheds, respectively) imply that shorter response times tended to have greater effects on hydrological drought events and lowered their Tr, and vice versa. These results provide new insight into propagation thresholds used for water resource planning and management, and may help to mitigate the effects of future climate change.

Knockdown of the SELENOK gene induces ferroptosis in cervical cancer cells.

Selenoprotein K (SELENOK) is one of the endoplasmic reticulum (ER) proteins that mainly functions in the regulation of ER stress, calcium flux, and antioxidant defense. Reactive oxygen species (ROS) is one of the key indicators of ferroptosis, and SELENOK inhibition could disrupt ROS balance, and consequently might cause ferroptosis. However, there are no previous studies about the mechanism of SELENOK in ferroptosis by regulating ROS. In this study, we report the effect of SELENOK inhibition on cell proliferation, viability, iron recycling-associated proteins, ROS, antioxidant enzymes, and lipid peroxidation of cervical cancer cells (HeLa cells). The results showed that ROS levels and iron-dependent lipid peroxidation were significantly enhanced, whereas cell viability and proliferation were significantly downregulated, and resulted in marked reductions in tumor size after SELENOK knockdown. SELENOK knockdown also caused steep decreases in glutathione peroxidase 4/glutathione levels and deterioration in ROS scavenging ability, and exacerbated ferroptosis in HeLa cells. Our findings elucidated that SELENOK knockdown could shrink tumor size by regulating ferroptosis, which might provide a theoretical basis for treating cervical cancer.

Research advances in role of angiogenesis in diabetic ulcer and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is one of the common complications of diabetes often occurring in the peripheral blood vessels of lower limbs or feet with a certain degree of damage. It has high morbidity and mortality, a long treatment cycle, and high cost. DU is often clinically manifested as skin ulcers or infections in the lower limbs or feet. In severe cases, it can ulcerate to the surface of tendons, bones or joint capsules, and even bone marrow. Without timely and correct treatment, most of the patients will have ulceration and blackening of the extremities. These patients will not be able to preserve the affected limbs through conservative treatment, and amputation must be performed. The etiology and pathogenesis of DU patients with the above condition are complex, which involves blood circulation interruption of DU wound, poor nutrition supply, and failure in discharge of metabolic waste. Relevant studies have also confirmed that promoting DU wound angiogenesis and restoring blood supply can effectively delay the occurrence and development of wound ulcers and provide nutritional support for wound healing, which is of great significance in the treatment of DU. There are many factors related to angiogenesis, including pro-angiogenic factors and anti-angiogenic factors. The dynamic balance between them plays a key role in angiogenesis. Meanwhile, previous studies have also confirmed that traditional Chinese medicine can enhance pro-angiogenic factors and down-regulate anti-angiogenic factors to promote angiogenesis. In addition, many experts and scholars have proposed that traditional Chinese medicine regulation of DU wound angiogenesis in the treatment of DU has broad prospects. Therefore, by consulting a large number of studies available, this paper expounded on the role of angiogenesis in DU wound and summarized the research advance in traditional Chinese medicine intervention in promoting the expression of angiogenic factors [vascular endothelial growth factor(VEGF), fibroblast growth factor(FGF), and angiopoietin(Ang)] which played a major role in promoting wound angiogenesis in the treatment of DU to provide ideas for further research and new methods for clinical treatment of DU.

Research progress in role of autophagy in diabetic wound healing and traditional Chinese medicine intervention / 中国中药杂志

Diabetic ulcer(DU) is a chronic and refractory ulcer which often occurs in the foot or lower limbs. It is a diabetic complication with high morbidity and mortality. The pathogenesis of DU is complex, and the therapies(such as debridement, flap transplantation, and application of antibiotics) are also complex and have long cycles. DU patients suffer from great economic and psychological pressure while enduring pain. Therefore, it is particularly important to promote rapid wound healing, reduce disability and mortality, protect limb function, and improve the quality of life of DU patients. By reviewing the relevant literatures, we have found that autophagy can remove DU wound pathogens, reduce wound inflammation, and accelerate ulcer wound healing and tissue repair. The main autophagy-related factors microtubule-binding light chain protein 3(LC3), autophagy-specific gene Beclin-1, and ubiquitin-binding protein p62 mediate autophagy. The traditional Chinese medicine(TCM) treatment of DU mitigates clinical symptoms, accelerates ulcer wound healing, reduces ulcer recurrence, and delays further deterioration of DU. Furthermore, under the guidance of syndrome differentiation and treatment and the overall concept, TCM treatment harmonizes yin and yang, ameliorates TCM syndrome, and treats underlying diseases, thereby curing DU from the root. Therefore, this article reviews the role of autophagy and major related factors LC3, Beclin-1, and p62 in the healing of DU wounds and the intervention of TCM, aiming to provide reference for the clinical treatment of DU wounds and subsequent in-depth studies.

TLC identification and quantitative determination of Shipi Xiaoshui gel plaster / 药学实践杂志

Objective To establish the method of thin layer chromatography (TLC) for identification and quantitative determination of Shipi Xiaoshui gel plaster. Methods TLC was adopted to qualitatively identify astragalus radix, plantaginis semen, curcumae rhizome, cinnamomi ramulus, polyporus umbellatus and akebia quinata. UPLC-MS was used to determine the content of astragaloside Ⅳ. Results TLC spots were clear and well-separated; RSDs of precision, reproducibility and stability tests were all lower than 3%, the linear range of astragaloside Ⅳ was 2.75-33 μg/ml (r=0.999 9, n=6), and the average recovery was 100.49% (RSD=1.98%, n=6). Conclusion The established method in this study is accurate, reliable and specific, which could be used for the quality control of Shipi Xiaoshui gel plaster.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Cost-effectiveness analysis of different screening modes for thalassemia in Hunan Province / 中华围产医学杂志

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Research progress in animal models of oral squamous cell carcinoma and common oral mucosal diseases / 中国基层医药

The pathogeneses of oral squamous cell carcinoma and most oral mucosal diseases are unclear. Therefore, establishing animal models with similar pathogeneses is significant for clinical prevention, diagnosis, and treatment of related diseases. At present, scholars have established animal models for different focuses. This paper aims to introduce the methods for establishing animal models of oral squamous cell carcinoma and common oral mucosal diseases, compare their advantages and disadvantages, and provide evidence for related basic research.

Effect of helicid on osteoarthritis of joint instability model and its mechanism / 中国药理学通报

Aim To study the therapeutic effect of helicid on osteoarthritis (OA) of joint instability model, and explore the mechanism of helicid in the treatment of OA. Methods A rat knee model of OA was established by the medial meniscectomy (MMx) method. After treatment with helicid, HE and safranin O/fast green staining methods were used to observe the his-topathological changes of rat knee articular cartilage; Western blot was used to detect the protein expression level of Trpvl in rat synovial tissue. Immunohistochemical staining was used to examine the expression of Trpvl in rat knee articular cartilage and synovial tissues. Results Helicid significantly slowed down the degeneration of rat knee articular cartilage as shown by HE and safranin O/fast green staining. Western blot results showed that helicid down-regulated the expression of Trpvl in rat synovial tissue examined. Immunohistochemical results showed that helicid significantly reduced the expression of Trpvl in both of knee articular cartilage and synovial tissues. Conclusions Helicid prominently decreases MMx-induced articular cartilage damage and cartilage matrix loss, thereby exerting a therapeutic effect on OA.

Comparative Study on Risk Assessment Tools for Clinical Trials in England, Germany and France / 中国医学伦理学

Risk assessment of clinical trials is of great significance to improve the quality of clinical trials. Through systematic comparative analysis of risk assessment tools for clinical trials in Britain, Germany and France, this paper found that the three countries’ risk assessment tools were consistent in terms of legal system guarantee and assessment process, but there were obvious differences in the basic risk classification and risk grading standards of clinical trials. Based on the experience of Britain, France and Germany, this paper proposed to improve the relevant regulations and documents of clinical trial risk management in China from the perspective of Chinese national conditions, further explore the factors affecting clinical trial risk, and develop and design clinical trial risk assessment tools with different discipline characteristics according to the specialties of the discipline to improve the quality and level of clinical trials.

Research Progress of Regulatory T Cells in the Pathogenesis of Multiple Myeloma --Review / 中国实验血液学杂志

The multiple myeloma (MM), the second most common hematologic malignancy, is malignant proliferative disease of plasma cells. Although the application of many targeted drugs has significantly prolonged the survival time of MM patients, it is still an incurable disease. In recent years, the immunosuppression caused by interaction between tumor microenvironment(TME) and tumor cells has attracted people's attention gradually. As a kind of immunosuppressive cells in TME, regulatory T cells (Treg) play an important role in the progress of MM. Treg is related to the proliferation and metastasis of tumors, and can lead to the progress of MM by promoting the angiogenesis and generating immunosuppressive TME. In this review, we briefly summarized the latest research progress on the impact of Treg on the pathogenesis of MM.

Value of Reduced Field-of-view DWI in Quantitative Assessment of Axial Spondyloarthritis / 中山大学学报(医学科学版)

ObjectiveTo investigate the value of reduced field-of-view DWI （r-FOV DWI） in quantitative assessment of axial spondyloarthritis. MethodsA total of 112 patients with chronic back pain or suspected axial spondyloarthritis receiving full field-of-view DWI （f-FOV DWI） and reduced field-of-view DWI （r-FOV DWI） from December 2019 to December 2021 were enrolled. Next， subjective image quality assessment （anatomical detail， artifacts， distortion， overall image quality） and objective image quality assessment including （signal to noise ratio and contrast to noise ratio） were conducted by two experienced radiologists. In addition， the Apparent Diffusion Coefficient （ADC） values of three groups （active group， inactive group， and control group） on the two DWI sequences were measured by the two radiologists， respectively. Finally， the consistency of measurement between the two researchers was evaluated and the differences in ADC values was compared. Results102 patients were included and were divided into three groups， including the active group （n=32）， inactive group （n=29）， and control group （n=41） according to ASAS diagnostic criteria. All subjective and objective image quality metrics were rated in favor of r-FOV DWI images compared with f-FOV DWI images ［overall image quality： DWI 4（3~4） vs. 3（3~3） and SNR： 6.58（5.05~10.38） vs. 4.46（2.37~10.04）， CNR： 2.04（-1.14~8.29） vs. 0.97（-8.19~7.12）；P＜0.05］. Inter-rater consistency of the two researchers were 0.60~0.74. According to the AUC curve， group inactive vs. control showed r-FOV DWI was better than f-FOV DWI. In other groups （lesion vs. control， active vs. inactive）， there were no differences between both sequences（P＜0.05）. ConclusionThe subjective image quality score and signal to noise ratio of r-FOV DWI were higher than those of f-FOV DWI， which could be used for quantitative assessment of axial spondyloarthritis.

Long-term Survival in Hospitalized Patients with Lung Cancer among Peasants in the Coal-producing Area in Eastern Yunnan, China / 中国肺癌杂志

BACKGROUND@#Xuanwei and Fuyuan are rural counties, located in the late Permian coal poly area of eastern Yunnan and western Guizhou, where lung cancer mortality rates are among the highest in the China, with similarity for both men and women, younger age at diagnosis and death, and higher in rural areas than in urban areas. In this paper, long-term follow-up of lung cancer cases in local peasants was conducted to observe their survival prognosis and its influencing factors.@*METHODS@#Data of patients diagnosed with lung cancer from January 2005 to June 2011, who had lived in Xuanwei and Fuyuan counties for many years, were collected from 20 hospitals at the local provincial, municipal and county levels. To estimate survival outcomes, individuals were followed up until the end of 2021. The 5-year, 10-year and 15-year survival rates were estimated using the Kaplan-Meier method. Survival differences were examined with Kaplan-Meier curves and Cox proportional hazards models.@*RESULTS@#A total of 3,017 cases were effectively followed up (2,537 peasants and 480 non-peasants). The median age at diagnosis was 57 years, and the median follow-up time was 122 months. During the follow-up period, 2,493 cases (82.6%) died. The distribution of cases by clinical stage was as follows: stage I (3.7%), stage II (6.7%), stage III (15.8%), stage IV (21.1%) and unknown stage (52.7%). Treatment at the provincial, municipal and county-level hospitals accounted for 32.5%, 22.2% and 45.3%, respectively, and surgical treatment was performed in 23.3% of cases. The median survival time was 15.4 months (95%CI: 13.9-16.1), and the 5-year, 10-year and 15-year overall survival rates were 19.5% (95%CI: 18.0%-21.1%), 7.7% (95%CI: 6.5%-8.8%) and 2.0% (95%CI: 0.8%-3.9%), respectively. Peasants with lung cancer had a lower median age at diagnosis, higher proportion residing in remote rural areas, and higher use of bituminous coal as a household fuel. They also have a lower proportion of early-stage cases, treatment at provincial or municipal hospitals, and surgical treatment, leading to poorer survival outcomes (HR=1.57). Even when considering factors such as gender, age, residential location, clinical stage at diagnosis, histological type, hospital level of service, and surgical intervention, peasants still exhibit a survival disadvantage. Multivariable Cox model analysis comparing peasants and non-peasants reveals that surgical intervention, tumor-node-metastasis (TNM) stage, and hospital level of service are common factors influencing survival prognosis, while the use of bituminous coal as a household fuel, hospital level of service and adenocarcinoma (compared to squamous cell carcinoma) are independent prognostic factors for lung cancer survival among peasants.@*CONCLUSIONS@#The lower lung cancer survival rate among peasants is associated with their lower socioeconomic status, lower proportion of early-stage diagnoses, lower proportion of surgical interventions, and treatment at provincial-level hospitals. Furthermore, the impact of other factors such as high-risk exposure to bituminous coal pollution on survival prognosis requires further investigation.

Glutathione S-transferase genetic polymorphisms and fluoride-induced reproductive toxicity in men with idiopathic infertility / 亚洲男科学杂志(英文版)

Male infertility caused by idiopathic oligoasthenospermia (OAT) is known as idiopathic male infertility. Glutathione S-transferase (GST) and fluoride may play important roles in idiopathic male infertility, but their effects are still unknown. Our study examined the relationship between GST polymorphisms and fluoride-induced toxicity in idiopathic male infertility and determined the underlying mechanism. Sperm, blood, and urine samples were collected from 560 males. Fluoride levels were measured by a highly selective electrode method, and GST genotypes were identified using polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Semen parameters, DNA fragmentation index (DFI), mitochondrial membrane potential (MMP), and oxidative stress (OS) biomarkers were statistically assessed at the P < 0.05 level. Compared with healthy fertile group, semen parameters, fluoride levels, OS biomarkers, sex hormone levels, and MMP and DFI levels were lower in the idiopathic male infertility group. For glutathione S-transferase M1 (GSTM1[-]) and glutathione S-transferase T1 (GSTT1[-]) or glutathione S-transferase P1 (GSTP1) mutant genotypes, levels of semen fluoride, OS, MMP, and DFI were considerably higher, and the mean levels of sperm parameters and testosterone were statistically significant in GSTM1(+), GSTT1(+), and GSTP1 wild-type genotypes. Both semen and blood fluoride levels were associated with oxidative stress in idiopathic male infertility patients. Elevated fluoride in semen with the genotypes listed above was linked to reproductive quality in idiopathic male infertility patients. In conclusion, GST polymorphisms and fluorine may have an indicative relationship between reproductive quality and sex hormone levels, and OS participates in the development of idiopathic male infertility.