Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases / 中华病理学杂志

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

Research on genetic model of keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the effect of genetic factors on the pathogenesis of keratoconus and its genetic model.METHODS: Genetic epidemiological methods were used to investigate the prevalence of keratoconus in 280 first-degree relatives of 100 patients with keratoconus who attended Henan Eye Hospital between July 2020 and April 2023. The heritability was estimated by Falconer regression method. The general genetic model was calculated using Penrose method, and the genetic model was confirmed by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory.RESULTS: The results showed that there were 16(5.714%)first-degree relatives of keratoconus probands suffering from keratoconus, and the heritability of keratoconus was(86.100±7.400)%. The S/q score calculated by the Penrose method was 35.348, which was near to 1/(q)1/2, suggesting that the genetic model of keratoconus might be polygenic inheritance. The expected prevalence in first-degree relatives of keratoconus patients by Falconer formula, Edwards approximation formula and the projection formula of San-Duo Jiang's threshold model theory were 5.900%, 7.714% and 5.700%, respectively, which showed no significant differences from the actual prevalence(5.714%), suggesting that keratoconus was a polygenetic disease.CONCLUSION:Genetic factors might play an important role in the pathogenesis of keratoconus, and keratoconus is a polygenetic disease.

Core in jingjin diagnosis and treatment: yizhi weishu / 中国针灸

Jingjin (muscle region of meridian) is a distal diagnosis and treatment system of the sinew/fascia disorders on the base of the concept of jin in TCM. Jin should be a particular palpable structure rather than a single anatomic structure with a specific distributing course. Yizhi weishu refers to a idea running through the whole process of diagnosis and treatment of sinew/fascia disorders, in which, the results, obtained by the overall observation and palpation of patient's sinew/fascia structure, are taken as the criteria of treatment. Yitong weishu (taking the sites of sensitivity or tenderness as the points) verifies this idea in practice. Under the guidance of yizhi weishu, through identifying the primary from the secondary, and regulating yin and yang, the spasticity and flaccidity of sinews/fascia can be cured and the induced diseases treated. The diagnosis and treatment system of jingjin, based on yizhi weishu, develops the original jingjin theory with vague concept involved, formulates a systematic thinking of treatment for sinew/fascia disorders and provides a new approach to clinical treatment.

Treatment of rheumatoid arthritis by injection of sinomenine solid lipid nanoparticles under a fluorescence endoscopic laser confocal microscope / 中国中药杂志

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.

Obesity is positively Associated with Depression in Older Adults: Role of Systemic Inflammation / 生物医学与环境科学（英文）

OBJECTIVE@#We aimed to explore the association between obesity and depression and the role of systemic inflammation in older adults.@*METHODS@#Adults ≥ 65 years old ( n = 1,973) were interviewed at baseline in 2018 and 1,459 were followed up in 2021. General and abdominal obesity were assessed, and serum C-reactive protein (CRP) levels were measured at baseline. Depression status was assessed at baseline and at follow-up. Logistic regression was used to analyze the relationship between obesity and the incidence of depression and worsening of depressive symptoms, as well as the relationship between obesity and CRP levels. The associations of CRP levels with the geriatric depression scale, as well as with its three dimensions, were investigated using multiple linear regressions.@*RESULTS@#General obesity was associated with worsening depression symptoms and incident depression, with an odds ratio ( OR) [95% confidence interval ( CI)] of 1.53 (1.13-2.12) and 1.80 (1.23-2.63), especially among old male subjects, with OR (95% CI) of 2.12 (1.25-3.58) and 2.24 (1.22-4.11), respectively; however, no significant relationship was observed between abdominal obesity and depression. In addition, general obesity was associated with high levels of CRP, with OR (95% CI) of 2.58 (1.75-3.81), especially in subjects free of depression at baseline, with OR (95% CI) of 3.15 (1.97-5.04), and CRP levels were positively correlated with a score of specific dimension (life satisfaction) of depression, P < 0.05.@*CONCLUSION@#General obesity, rather than abdominal obesity, was associated with worsening depressive symptoms and incident depression, which can be partly explained by the systemic inflammatory response, and the impact of obesity on depression should be taken more seriously in the older male population.

Development of the Scientific, Transparent and Applicable Rankings (STAR) tool for clinical practice guidelines / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability.@*METHODS@#This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability.@*RESULTS@#STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min.@*CONCLUSION@#The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.

Study on the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng / 中国针灸

To explore the methods of the explicitation of implicit knowledge and the construction of knowledge graph on moxibustion in medical case records of ZHOU Mei-sheng's Jiusheng. The medical case records data of Jiusheng was collected, the frequency statistic was analyzed based on Python3.8.6, complex network analysis was performed using Gephi9.2 software, community analysis was performed by the ancient and modern medical case cloud platform V2.3.5, and analysis and verification of correlation graph and weight graph were proceed by Neo4j3.5.25 image database. The disease systems with frequency≥10 % were surgery, ophthalmology and otorhinolaryngology, locomotor, digestive and respiratory systems. The diseases under the disease system were mainly carbuncle, arthritis, lumbar disc herniation and headache. The commonly used moxibustion methods were fumigating moxibustion, blowing moxibustion, direct moxibustion and warming acupuncture. The core prescription of points obtained by complex network analysis included Yatong point, Zhiyang(GV 9), Sanyinjiao(SP 6), Dazhui(GV 14), Zusanli(ST 36), Lingtai(GV 10), Xinshu(BL 15), Zhijian point and Hegu(LI 4), which were basically consistent with high-frequency points. A total of 6 communities were obtained by community analysis, corresponding to different diseases. Through the analysis of correlation graph, 13 pairs of strong association rule points were obtained. The correlation between Zhiyang(GV 9)-Dazhui(GV 14) and Yatong point-Lingtai(GV 10) was the strongest. The acupoints with high correlation with Yatong point were Zhiyang(GV 9), Lingtai(GV 10), Dazhui(GV 14), Zusanli(ST 36) and Sanyinjiao(SP 6). In the weight graph of the high-frequency disease system, the relationship of the first weight of the surgery system disease was fumigating moxibustion-carbuncle-Yatong point, and the relationship of the first weight of the ophthalmology and otorhinolaryngology system disease was blowing moxibustion-laryngitis-Hegu (LI 4). The results of correlation graph and weight graph are consistent with the results of data mining, which can be used as an effective way to study the knowledge base of moxibustion diagnosis and treatment in the future.

A summary on surveillance system of occupational disease under the framework of National Health Insurance Informatization Project / 中华劳动卫生职业病杂志

The surveillance of occupational disease has entered a new stage ofdevelopment, with the implementation of the national health informatization project. To improve the efficiency and quality of occupational disease monitoring information reporting in this paper, the system architecture and related management regulations, as long as the major changes and achievement of "surveillance system of occupational disease and health hazards information" under the framework of National Health Insurance Informatization Project were elaborated. The deficiencies existing in the system were analyzed, and expectation for the construction of the occupational disease surveillance system was addressed.

Investigation and analysis of late reporting and under-reporting of occupational diseases from 2018 to 2020 in China / 中华劳动卫生职业病杂志

Objective: To understand the late reporting and the under-reporting of occupational disease from 2018 to 2020 in China and analyze the causes, so as to provide scientific evidence for improving the quality of occupational disease reports in China, timely acquiring the incidence of occupational disease, and assessing the occupational hazards. Methods: From May to December 2021, A total of 320 occupational disease diagnostic institutions were selected for investigation. The original documents of occupational disease diagnosis cases from 2018 to 2020 were compared with the online reported cases, and late reported and under-reported cases of occupational disease were analyzed. Results: A total of 32207 diagnosed cases from 2018 to 2020 were investigated, including 28934 confirmed cases and 3273 cases without occupational disease. The overall late reported rate and under-reported rate of confirmed cases were 20.2% and 2.1%, respectively. There were significant differences in the rate of late reporting and under-reporting of occupational diseases in different regions and different types of diagnostic institutions (P<0.001). The southwest region had the highest rates of late reporting and under-reporting, 61.6% and 7.9% respectively. The late reported rate of all kinds of occupational diseases was about 15.0%, and the under-reported rate was from 1.5.0% to 5.0%. Conclusion: At present, the phenomenon of late reporting and under-reporting occupational diseases is still obvious. It is necessary to strengthen the inspection of occupational disease reporting, improve the quality of occupational disease reporting, and provide scientific basis for the formulation of occupational disease prevention and control policies.

The sleep condition and its association with cognitive function of the elderly in six provinces of China / 中华预防医学杂志

Objective: To analyze the association between sleep duration and cognitive function of the elderly in six provinces of China. Methods: Based on the cross-sectional survey data of the elderly from the Healthy Ageing Assessment Cohort Study in 2019, 4 644 participants' sociodemographic and economic indicators, lifestyle, prevalence of major chronic diseases, and sleep status, including night-time sleep duration, daytime sleep duration and insomnia, were collected by questionnaires. Cognitive function was evaluated by the Mini-Mental State Examination. Multivariate logistic regression was used to analyze the association between night-time sleep duration, daytime sleep duration and cognitive function. Results: The mean age of 4 644 respondents was (72.3±5.7) years, and 2 111 of them were males (45.5%). The mean total daily sleep time of the elderly was (7.9±1.9) hours, and the proportion of those who slept less than 7.0, 7.0-8.9 and≥9.0 hours was 24.1% (1 119), 42.1% (1 954) and 33.8% (1 571), respectively. The mean sleep time at night was (6.9±1.7) hours. About 23.7% (1 102) of the elderly did not sleep during the day, and the mean duration of the elderly who slept during the day was (78±51) minutes. Among the elderly with insomnia, 47.9% were still satisfied with their sleep quality. The mean value of MMSE score of 4 644 respondents was (24.5±5.3), and the cognitive impairment rate was 28.3% (1 316). The results of multivariate logistic regression model analysis showed that the OR (95%CI) value of the risk of cognitive impairment in older people who did not sleep, slept for 31 to 60 minutes and slept more than one hour was 1.473 (1.139 to 1.904), 1.277 (1.001 to 1.629) and 1.496 (1.160 to 1.928), respectively, compared with those who slept for 1 to 30 minutes during the daytime. Compared with those who slept for 7.0‒8.9 hours at night, the OR (95%CI) value of the risk of cognitive impairment in older people who slept more than 9.0 hours was 1.239 (1.011 to 1.519). Conclusion: The cognitive function is related to sleep duration in the Chinese elderly.

PK/PD model of Chuanxiong gel plaster in treatment of rheumatoid arthritis / 中国中药杂志

In this experiment, the PK/PD fitting model of Chuanxiong(Chuanxiong Rhizoma) in the treatment of rheumatoid arthritis was established in the form of acupoint combined with external application gel paste. Firstly, the rheumatoid arthritis model was induced by ovalbumin, and the articular fluid of rabbits was extracted by microdialysis. The pharmacokinetic process of Chuanxiong in rabbit articular fluid was analyzed by UPLC-MS/MS, and the pharmacokinetic model was established. The pharmacodynamic effects of Chuanxiong on inflammatory factors IL-1β, TNF-α, and IL-6 were analyzed by enzyme-linked immunosorbent assay(ELISA). The pharmacodynamic model was established, and the PK/PD model was obtained by fitting the data of pharmacokinetics and pharmacodynamics. The results of pharmacokinetics showed that the concentration of ligustrolide A in the articular cavity by drug administration on classical acupoint Zusanli(ST 36) was higher than that by Yanglingquan(GB 34), which reflected the advantage of typical acupoint, while ligustrazine concentration was higher after administration through Yanglingquan than through Zusanli, which was different from the traditional acupoint theory. The results of pharmacodynamics showed that the drug had lag effect. The PK/PD model was constructed by fitting the data. When IL-1β was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=115.28C_e/(3 316.72+C_e), E=108.73C_e/(2 993.47+C_e), and E=101.34C_e/(3 028.51+C_e). When TNF-α was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=68.31C_e/(3 285.16+C_e), E=59.27C_e/(2 919.86+C_e), and E=53.61C_e/(2 862.87+C_e). When IL-6 was taken as the efficacy index, the PK/PD models of Chuanxiong in typical acupoint Zusanli group, atypical acupoint Yanglingquan group, and non-acupoint group were E=59.92C_e/(3 461.17+C_e), E=58.34C_e/(2 723.51+C_e), and E=49.17C_e/(2 862.76+C_e). The parameters showed that there were significant differences in E_(max), EC_(e50) and k_(eo). The analysis of data found that the PK/PD fitting effect of Zusanli, a typical acupoint, was the best, which proved that it was still the best site for drug administration. To sum up, it shows that there may be bidirectional selectivity between drugs and acupoints.

Construction and mechanism of dry eye model in mice with ocular surface iron overload / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish a dry eye mouse model of iron overload by intraperitoneal injection of iron dextran and preliminarily explore its possible mechanism.METHODS: A total of 40 male C57BL/6 mice(taking the right eye as the experimental eye)were divided into 4 groups by random number table method: There were 10 mice in the control group, each time by intraperitoneal injection of 0.2mL of normal saline; Low-dose group, middle-dose group and high-dose iron group with 10 mice in each group were the model group. Each time, 0.2mL of iron dextran solution with concentrations of 12.5, 25, and 50 mg/mL was injected intraperitoneally. One injection 3d for a total of 28d. We observed the ocular surface inflammation index, corneal fluorescein staining, tear break-up time(BUT)and Schimer I test(SIt)on the 7, 14 and 28d after injection and evaluated the degree of dry eye and ocular surface inflammation. After 28d, the mice were sacrificed for cornea, conjunctiva and lacrimal glands tissue for HE staining, Prussian blue staining and tissue iron detection, to evaluate the inflammatory reaction and iron overload. The expression of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and matrix metallo proteinase-9(MMP-9)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS: Compared with the control group, the mice in the model group showed a series of dry eye symptoms, the inflammation index of ocular surface in mice were increased, the score of corneal fluorescein staining increased, the BUT shortened and the amount of tear secretion decreased(all P&#x003C;0.05). The cornea, conjunctiva and lacrimal gland tissues of the mice were damaged to varying degrees, the iron deposition on the eye surface of the model group was more serious than that of the control group, and the iron content of the tissue was significantly increased than the control group(all P&#x003C;0.01). The contents of inflammatory factors(IL-1β, TNF-α, MMP-9)in the cornea, conjunctiva and lacrimal gland tissue of the mice in the model group were significantly higher than those of the control group(all P&#x003C;0.01). With the increase of injection time and concentration of iron dextran, the degree of dry eye and ocular surface inflammation in mice gradually increased. CONCLUSION: The mouse iron overload dry eye model was successfully established by intraperitoneal injection of iron dextran, the mechanism may be related to the ocular surface inflammation aggravated by iron overload.

Efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore whether efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization. METHODS: A total of 50 healthy C57BL/6 male mice aged 6-8wk were randomly divided into normal control group, iron group, inhibitor group, enhancer group and solvent control group, with 10 mice in each group. The normal control group was injected intraperitoneally with 0.2mL of normal saline, and the other groups were injected intraperitoneally with 50mg/mL iron dextran of 0.2mL, once every 3d. From the 14d, the inhibitor group, the enhancer group and the solvent control group were injected intraperitoneally with the same volume(0.2mL)50mg/kg XMD8-92, 10mg/kg simvastatin and 50% DMSO solvent once a day, respectively. The anterior segment of the eyes was observed under slit lamp microscope on the 7, 14, 28d after intraperitoneal injection, and the ocular surface inflammation index and corneal fluorescein staining score were evaluated. The cornea, conjunctiva and lacrimal gland tissues were taken at 28d for the HE staining and immunofluorescence staining, and RT-PCR were used to detect the expression of macrophage polarization related indexes(CD86, CD206, iNOS, Arg-1); Western blot were used to detect the expression of efferocytosis related signal factors(Gas6, MerTK); ELISA was used to detect the expression of inflammatory factors(IL-1β, TNF-α, MMP-9).RESULTS: After injection for 28d, compared with the normal control group, the ocular surface inflammatory index and corneal fluorescein staining score were increased in the iron group and the solvent control group. HE staining showed incomplete corneal epithelium, reduced conjunctival goblet cells, unclear lacrimal gland structure and relatively disordered arrangement of cells. In all tissues, the expressions of polarization related indexes of M1 macrophages such as CD86 and iNOS were up-regulated, while those of M2 macrophages such as CD206 and Arg-1 were down-regulated, and the expressions of inflammatory factors such as IL-1β, TNF-α and MMP-9 were up-regulated(all P&#x003C;0.05). Compared with the iron group and the solvent control group, the ocular surface inflammation index and corneal fluorescein staining score of the inhibitor group were further increased. HE staining showed obvious exfoliation of corneal epithelium, further decrease or even disappearance of conjunctival goblet cells, disorder of lacrimal gland structure and irregular arrangement of cells. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was down-regulated(all P&#x003C;0.05), the expression of polarization related indexes of M1 macrophages such as CD86 and iNOS and the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 were further up-regulated(all P&#x003C;0.05). But the ocular surface inflammation index and corneal fluorescein staining score decreased in the enhancer group. HE staining showed the integrity of corneal epithelial, the increase of conjunctival goblet cells and the improvement of lacrimal gland structure and morphology. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was up-regulated(all P&#x003C;0.05), and the expression of polarization related indexes of M2 macrophages such as CD206 and Arg-1 was up-regulated, while the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 was down-regulated(all P&#x003C;0.05). CONCLUSION: High-iron environment induces macrophages polarize to M1, which aggravates ocular surface inflammation and tissue damage. Efferocytosis by regulating the polarization of macrophages impact the occurrence of ocular surface inflammation in high-iron environment.

Proteinuria associated with hookworm infection: a case report / 中国血吸虫病防治杂志

As a common soil-borne nematode, hookworm is mainly parasitized in the intestine, and the clinical manifestations of hookworm infections mainly include gastrointestinal symptoms and iron-deficiency anemia. In addition, hookworm may be also parasitized in other organs in addition to gastrointestinal system, resulting in development of disorders in other systems. Proteinuria caused by hookworm infections is rare and easy to be misdiagnosed in clinical practices. Hereby, the diagnosis and treatment of a case of proteinuria associated with hookworm infections was reported, in order to increase the understanding of hookworm infection-associated proteinuria among clinicians.

Clinicopathological features and prognosis of high-grade B-cell lymphoma with MYC and bcl-2 and/or bcl-6 rearrangements / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.

Kang-Ai Injection Inhibits Gastric Cancer Cells Proliferation through IL-6/STAT3 Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms underlying the proliferative inhibition of Chinese herbal medicine Kang-Ai injection (KAI) in gastric cancer cells.@*METHODS@#Gastric cancer cell lines MGC803 and BGC823 were treated by 0, 0.3%, 1%, 3% and 10% KAI for 24, 48 and 72 h, respectively. The cell proliferation was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The apoptosis and cell cycle were evaluated by flow cytometry. Interleukin (IL)-6 mRNA and protein expression levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immune sorbent assay (ELISA), respectively. The protein expression levels of cyclin A, cyclin E, cyclin B1, cyclin D1, p21, retinoblastoma (RB), protein kinase B (AKT), extracellular regulated protein kinases (ERK), signal transducer and activator of transcription (STAT) 1 and STAT3 were detected by Western blot.@*RESULTS@#KAI inhibited the proliferation of MGC803 and BGC823 gastric cancer cells in dose- and time-dependent manner. After treated with KAI for 48 h, the proportion of G1 phase was increased, expression level of cyclin D1 and phosphorylation-RB were down-regulated, whereas the expression of p21 was up-regulated (all P<0.01). Furthermore, 48-h treatment with KAI decreased the phosphorylation level of STAT3, inhibited the mRNA and protein expressions of IL-6 (all P<0.01). IL-6 at dose of 10 ng/mL significantly attenuated the proliferative effect of both 3% and 10% KAI, and recovered KAI-inhibited STAT3 phosphorylation and cyclin D1 expression level (all P<0.01).@*CONCLUSION@#KAI exerted an anti-proliferative function by inhibiting IL-6/STAT3 signaling pathway followed by the induction of G1 phase arrest in gastric cancer cells.

Study on antioxidation and inhibiting melanin production of tetrahydrocurcumin and its mechanism / 中国药理学通报

Aim To evaluate the antioxidant effect of tetrahydrocurcuminoids(THC)and its effect on melanin production,and to explore its mechanism of inhibiting melanin production.Methods Human immortalized epidermal cell(HaCaT cell)model was used to evaluate the antioxidant activity.The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX)and lactate dehydrogenase(LDH)in HaCaT cells were detected by ELISA.Total antioxidant activity of THC was detected by DPPH and T-AOC methods.Mouse melanoma cell model B16F10 was used on the experiment of inhibition of melanin production.The effect of THC on the proliferation activity of mouse B16F10 cells was determined by CCK8 assay.The content of melanin and tyrosinase activity in B16F10 cells were determined by NaOH lysis assay and dopamine oxidation assay,respectively.The effect of THC on B16F10 cell migration was investigated by scratch assay,and the expression of melanin production-related protein MITF was determined by Western blot.Results THC could increase the levels of SOD and GSH-Px in HaCaT cells,reduce the content of LDH,and increase the scavenging rate of DPPH free radical and the reducing ability of Fe3+.THC could inhibit the proliferation and migration of mouse B16F10 cells,reduce the content of melanin in B16F10 cells,reduce the activity of tyrosinase,and inhibit the expression of MITF.Conclusions Tetrahydrocurcumin has antioxidant effect and can inhibit melanin production,and its mechanism is related to inhibiting MITF expression.

Study on mechanism of Gualou Xiebai Banxia decoction in treating dynamic atherosclerosis based on network pharmacology and in vitro study / 中国药理学通报

Aim To explore the molecular mechanism atherosclerosis by network pharmacology and in vitro of Gualou Xiebai Banxia decoction in the treatment of study.Methods All chemical constituents and targets of Gualou Xiehai Banxia decoction were retrieved from TCMSP database.OMIM, DrugBank and TTD databas¬es were searched with "atherosclerosis" as the search term , and the related targets of atherosclerosis were ob¬tained after eliminating duplicate options.DAVID da¬tabase was used for GO and KEGG pathway enrichment analysis of intersection targets.Finally, the analysis results were confirmed in the ox-LDL induced human aortic endothelial cell injury model.Results A total of 30 active compound molecules in Gualou Xiebai Banxia decoction and 78 potential targets for the treat¬ment of atherosclerosis were retrieved.The therapeutic targets were mainly related to inflammatory pathway, apoptosis and so on.(3-sitosterol was chosen as a po¬tential pharmacodynamic molecule for the treatment of atherosclerosis to verify the correctness of the results of network pharmacological analysis.In vitro experiments showed that, (3-sitosterol could prevent ox-LDL in¬duced apoptosis of human aortic endothelial cells and significantly reduce the level of IL-ip, 1L-6 and TNF- cx in cell culture medium, and protein expression of p- NF-kB/NF-kB, 1L-1 p, 1L-6 and TNF-a in cells.Conclusions The treatment effect of Gualou Xiebai Banxia decoction on atherosclerosis is mainly mediated by regulating inflammation, apoptosis and other path¬ways through multi-component effect, multiple targets and multiple pathways.

Effect of Tibetan medicine E-se on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes / 中国药理学通报

Aim To evaluate the effect of E-se extract on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes anrl explore its mechanism.Methods Ten C57/6J mice were assigned to a normal control group.Fifty KK-Ay model mice were randomly divided into model group, positive control group ( rosiglita- zone, 2.67 mg • kg 1 ), and low- ( 0.75 g • kg 1 ) , medium- ( 1.50 g • kg 1 ) , and high-dose ( 3.00 g • kg ') E-se groups, with 10 mice in each group.All mice were measured for body weight and fasting blood glucose weekly, insulin tolerance on the 32nd day, and insulin after the last administration on the 35th day, and the insulin resistance/sensitivity indexes were calculated.The pancreas was stained by hematoxylin- eosin ( HE ).Islet cell apoptosis was detected by TUNEL staining.Glucagon-like peptide-1 ( GLP-1 ) was detected by immunohistochemistry.Results j j Compared with the model group, the E-se groups showed reduced body weight, fasting blood glucose, serum insulin concentration, and insulin resistance in¬dex, elevated insulin sensitivity index, decreased le¬sion grading score of pancreatic tissues and apoptosis percentage of islet cells, and increased content of GLP- 1 protein in pancreatic tissues.Conclusions E-se ex¬tract can improve insulin resistance by reducing serum insulin level, inhibiting islet cell apoptosis, and in¬creasing the sensitivity of the body to insulin.

Establishment of a rat silicosis model via non-exposed tracheal instillation in combination with a ventilator / 中国职业医学

@#Objective - To establish a new non exposed intratracheal instillation method for establishing a rat silicosis model. Methods ， The specific pathogen free SD rats were randomly divided into control group and experimental group with ten rats in ， each group. Rats in the control group were given 1.0 mL of 0.9% sodium chloride solution and rats in the experimental group - were given 1.0 mL of silica suspension with a mass concentration of 50 g/L adopting to the one time intratracheal instillation ， - ， method and then followed by ventilator assisted ventilation immediately. When the tidal volume stabilized at 2.0 mL the ventilator was removed and the tracheal intubation was pulled out. Five rats in each group were sacrificed after two and four ， - Results weeks after modeling and hematoxylin eosin staining and Masson staining of lung tissue were performed. There was ， ， no death in the two groups of rats during the experiment. After two and four weeks the control group had normal lung structure ， ， ， normal alveolar cavity size no inflammatory cell infiltration thin alveolar wall only a small amount of collagen distribution ， around the lung interstitium and bronchus. At the second week of modeling the alveolar wall of the rats in the experimental ， ， ， group was slightly thickened interstitial lymphocytes and macrophages were infiltrated slight hyperplasia was found and a ， small amount of fibroblasts were visible. At the 4th week of modeling the alveolar wall of the rats in the experimental group was ， ， ， ， significantly thickened fibrous nodules were formed and fibroblasts fibrocytes collagen fibers were significantly increased. Conclusion - The combination of ventilator and non exposed intratracheal instillation method can be used to successfully ， ， . establish a rat silicosis model which is simple safe and effective