Efficacy and safety of interventional therapy combined with drug injection under bronchoscope in the treatment of central non-small cell lung cancer / 中国临床药理学与治疗学

AIM: To evaluate the efficacy and safety of interventional therapy combined with tumor drug injection under bronchoscope for central non-small cell lung cancer (NSCLC). METHODS: Sixty-four patients who met the test admission criteria were randomly assigned to the experimental group and the control group according to the ratio of 1:1, and were given bronchoscopic interventional therapy combined with local drug injection of recombinant human endostatin combined with platinum-containing dual-drug chemotherapy and platinum-containing dual-drug alone, respectively. The curative efficiency and safety of the two groups were compared. RESULTS: Compared with the control group, the KPS score, dyspnea grading were significantly improved (P<0.05). The effective rate of the test group was 78.12%, which was higher than 37.5% in the control group, the difference between the two groups was significant (P<0.05). Moreover, there was also a significant difference in the 1-year survival rate between the experimental group and the control group (P<0.05). CONCLUSION: The treatment of central NSCLC by interventional therapy combined with tumor drug injection through fiberoptic bronchoscope has obvious clinical efficacy, which can effectively alleviate the clinical symptoms and improve the quality of life of patients. There is no significant difference in adverse reactions between the two groups, and is worthy of popularization and application.

Apalutamide for metastatic castration-sensitive prostate cancer: final analysis of the Asian subpopulation in the TITAN trial / 亚洲男科学杂志(英文版)

The final analysis of the phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial showed improvement in overall survival (OS) and other efficacy endpoints with apalutamide plus androgen deprivation therapy (ADT) versus ADT alone in patients with metastatic castration-sensitive prostate cancer (mCSPC). As ethnicity and regional differences may affect treatment outcomes in advanced prostate cancer, a post hoc final analysis was conducted to assess the efficacy and safety of apalutamide in the Asian subpopulation. Event-driven endpoints were OS, and time from randomization to initiation of castration resistance, prostate-specific antigen (PSA) progression, and second progression-free survival (PFS2) on first subsequent therapy or death. Efficacy endpoints were assessed using the Kaplan-Meier method and Cox proportional-hazards models without formal statistical testing and adjustment for multiplicity. Participating Asian patients received once-daily apalutamide 240 mg ( n = 111) or placebo ( n = 110) plus ADT. After a median follow-up of 42.5 months and despite crossover of 47 placebo recipients to open-label apalutamide, apalutamide reduced the risk of death by 32% (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.42-1.13), risk of castration resistance by 69% (HR: 0.31; 95% CI: 0.21-0.46), PSA progression by 79% (HR: 0.21; 95% CI: 0.13-0.35) and PFS2 by 24% (HR: 0.76; 95% CI: 0.44-1.29) relative to placebo. The outcomes were comparable between subgroups with low- and high-volume disease at baseline. No new safety issues were identified. Apalutamide provides valuable clinical benefits to Asian patients with mCSPC, with an efficacy and safety profile consistent with that in the overall patient population.

Salvianolic acid A contributes to cartilage endplate cell restoration by regulating miR-940 and miR-576-5p / 中国骨伤

OBJECTIVE@#To investigate whether Salvianolic acid A (SAA) can restore cartilage endplate cell degeneration of intervertebral discs and to identify the mechanism via regulation of micro-RNA.@*METHODS@#Cartilage endplate cells were isolated from lumbar intervertebral disc surgical samples and were treated with serum containing a series of concentrations of SAA (2, 5, and 10 ?M) for 24, 48, and 72 h to identify a proper dose and treatment time of SAA. The effect SAA on interlenkin-1β (IL-1β)-induced extracellular matrix degradation of cartilage endplate cells were analyzed by Alcian blue staining and assessment of the expression levels of ADAMTS-5, MMP3 and Col2a1. Further, the potential target miRNAs were preliminarily screened by micro-RNA sequencing combining qRT-PCR and Western blot, and then, the miRNAs mimics and inhibitors were used to verify the regulatory effect of SAA on potential target miRNAs.@*RESULTS@#The 10 μM SAA treatment for 48 h significantly enhanced the viability of cartilage endplate cells, and increased Col2a1 expression and glycosaminoglycan accumulation that were repressed by IL-1β, and reduced the effect of IL-1β on ADAMTS-5, and MMP3. Screening analysis based on micro-RNA sequencing and Venny analysis identified the downstream micro-RNAs, including miR-940 and miR-576-5p. Then, the miR-940-mimic or miR-576-5p-mimic were transfected into CEPCs. Compared with the SAA group, the expression of ADAMTS-5 and MMP3 increased significantly and the expression of COL2A1 obviously decreased after overexpression of miR-940 or miR-576-5p in CEPCs.@*CONCLUSION@#Salvianolic acid A attenuated the IL-1β-induced extracellular matrix degradation of cartilage endplate cells by targeting regulate the miR-940 and the miR-576-5p.

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.

Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis / 中国中药杂志

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Renal injury induced by lenvatinib in advanced hepatocellular carcinoma treated with multi- drug combination: a case report and literature review / 中华肾脏病杂志

The article reported one case of renal damage caused by lenvatinib in the treatment of advanced primary liver cancer. The patient was a 63-year-old male who was admitted to the hospital due to "liver cancer for 4 years, blood pressure elevation for nearly 2 years, and edema for 7 months". During the treatment of liver tumors with atezolizumab combined with lenvatinib, blood pressure increased and renal insufficiency aggravated progressively. Pathological light microscopy of renal biopsy showed endothelial cell lesion and tubulointerstitial damage, and electron microscopy showed moderate proliferation of mesangial cells and deposition of mesangial matrix. There were many agglomerated low-electron density deposits in the mesangial area, and a small amount of electron dense deposits in the subendothelium. The pathological diagnosis was endothelial cell disease (thrombotic microangiopathy) and secondary focal segmental glomerulosclerosis. Renal injury was considered as secondary to lenvatinib. After discontinuing lenvatinib and giving angiotensin receptor antagonist treatment, blood pressure was normal, urine protein turned negative, and renal function improved significantly after 8 months of outpatient follow-up.

Fanconi syndrome secondary to primary biliary cholangitis: a case report / 中华肾脏病杂志

Primary biliary cirrhosis/cholangitis is an autoimmune disease. Renal tubular acidosis is a common form in PBC cases, but Fanconi syndrome is rarely reported. The paper reported a 66-year-old female patient with fatigue, renal insufficiency and elevated bile duct enzymes. The patient presented with type 2 proximal renal tubular acidosis and complete Fanconi syndrome. Laboratory examinations showed high-titer-positive anti-mitochondrial antibodies, elevated serum IgM, and type 3 cryoglobulinemia. Renal biopsy revealed interstitial nephritis, and electron micrographs showed abnormal mitochondria in proximal tubular epithelial cells. The patient's renal function ameliorated, and acid-base imbalance and electrolyte disturbances were corrected after high-dose glucocorticoid treatment.

Feasibility of MRI assisting early diagnosis of midfoot ligament and tendon injuries / 中华全科医师杂志

Objective:To explore the feasibility of MRI to assist the early diagnosis of midfoot tendon and ligament injuries.Methods:Fifty-two patients with midfoot ligament and tendon injuries who visited Beijing Jishuitan Hospital from September 2016 to December 2021 were enrolled in the study, and 20 healthy volunteers were recruited as controls. All participants underwent mid foot coronal (short axis), sagittal, and axial (long axis) MRI T1 weighted imaging and proton fat suppression sequence examination. The MRI images were evaluated by 2 senior radiologists independently.Results:The consistency of the two radiologists in diagnosis of tendons, ligaments, bones, and soft tissues were good ( κ=0.916, 0.896, and 0.893, respectively). The tendons and ligaments of the midfoot in 20 healthy volunteers (40 feet) showed uniform bands of varying thickness with slightly low signal intensity; the anterior tibial tendon showed a thin line shape, the posterior tibial tendon showed a slightly thick band with uniform low signal intensity, and the calcaneonavicular ligament showed a thin line-like low signal intensity running in different directions. In 52 patients with midfoot tendon and ligament injuries, 18 had anterior tibial tendon injuries, 20 had posterior tibial tendon injuries, and 14 had calcaneonavicular ligament injuries. The injured tendon or ligament was characterized by uneven thickness, blurred edges, and continuous interruption on T1WI sequence, uneven enhancement of signal in the tendon or ligament running area on PD-FS sequence, accumulation of fluid in the tendon sheath, and partial tearing. The partial tear showed discontinuity and thickening of tendons, while the complete tear showed that the tendons were interrupted and retracted, the fiber structure disappeared and was filled with liquid, and the surrounding soft tissue edema was present. Conclusion:MRI can clearly display the course and anatomical structure of the attachment end of the midfoot tendon and ligament, which may assist in early diagnosis of midfoot tendon and ligament injuries.

Value of dual-layer spectral detector CT in evaluating the intramedullary invasion of limb osteosarcoma / 中华放射学杂志

Objective:To explore the optimal keV value of the virtual monoenergetic image (VMI) for displaying the osteosarcoma by using the dual-layer spectral detector CT and to evaluate its application value in determining the extent of intramedullary invasion of osteosarcoma.Methods:From August 2021 to August 2022, 57 patients with conventional osteosarcoma of long bone confirmed by biopsy in Beijing Jishuitan Hospital, Capital Medical University were retrospectively analyzed. All patients completed dual-layer spectral CT enhanced examination before limb salvage surgery, and tumor segment resection specimens were obtained after surgery. Conventional 120 kVp image and VMI of 40, 50, 60, 70 and 80 keV were obtained by spectral CT examination, and the CT values of tumors, image noise were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the corresponding images were calculated. The objective evaluation among the six groups of images were assessed with the Friedman test, and then determined the optimal keV value. The maximum distance between the intramedullary boundary of osteosarcoma and the adjacent articular surfaces was measured on the best keV VMI and the tumor segment resection specimens. The Wilcoxon signed rank test was used to find the differences and the Spearman correlation analysis was used to evaluate the correlation between the distance measured from the best keV VMI and the specimens.Results:There were significant differences in CT value, image noise, SNR and CNR between 40-80 keV VMI and 120 kVp conventional CT images ( P<0.05). The CT value, SNR and CNR of 40 and 50 keV VMI were better than 120 kVp ( P<0.001). The 50 keV VMI was chosen as the best keV VMI to measure the intramedullary extent of osteosarcoma. The distance measured from 50 keV VMI was 103.9 (80.4, 131.4) mm, while the distance measured from specimens was 113.5 (94.0, 142.0) mm, and the difference was statistically significant ( Z=-5.76, P<0.001). The 50 keV VMI measurements in 51 patients were smaller than the gross specimens, which underestimated the tumor intramedullary extent, with the difference was 11.1 (6.6, 13.8) mm. The Spearman correlation analysis demonstrated a high positive correlation of distance measured on gross specimens with the 50 keV VMI ( r s=0.960, P<0.001). Conclusions:Dual-layer spectral detector CT with 50 keV VMI is the best image to show the limb osteosarcoma. Compared with gross specimens, the distance measured from CT underestimated the intramedullary invasion range of limb osteosarcoma about 10 mm, but the two show a good correlation.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Comparison on Performance of Quantitative Ultrasound and Dual-Energy X-ray Absorptiometry in Evaluating Bone Health of Adults Aged 18-40 Years / 中国医学科学院学报

Objective To compare the consistency of quantitative ultrasound(QUS)and dual-energy X-ray absorptiometry(DXA)in measuring bone mineral density(BMD)of adults aged 18-40 years in Guangzhou and evaluate the diagnostic value of QUS for identifying low bone mass.Methods DXA was employed to measure the BMD and QUS to measure the speed of sound(SOS)in 731 participants.The Bland-Altman analysis was performed to evaluate the consistency of Z scores between SOS and BMD.With the BMD Z ≤-2.00 as the diagnostic criterion for low bone mass,the receiver operating characteristics curve of QUS was established,and the area under the curve(AUC)and the sensitivity,specificity,and correct diagnostic index for the optimal cut-off of SOS Z score were calculated.Results The results of Bland-Altman analysis showed that the mean differences in the Z scores of SOS and BMD in males and females were 1.27(-0.94 to 3.47)and 0.93(-1.33 to 3.18),respectively.The AUC of SOS Z score in the diagnosis of low bone mass in males and females was 0.734(95%CI=0.380-0.788)and 0.679(95%CI=0.625-0.732),respectively.In males,the optimal cut-off of SOS Z score for low bone mass was -0.35,with the sensitivity,specificity,and correct diagnostic index of 64.1%,68.6%,and 0.327,respectively.In females,the optimal cut-off value of SOS Z scores for low bone mass was -1.14,with the sensitivity,specificity,and correct index of 73.9%,54.8%,and 0.285,respectively.Conclusion QUS and DXA show poor consistency in the diagnosis of BMD in the adults aged 18-40 years in Guangzhou,while QUS demonstrates an acceptable value in identifying low bone mass.

Association Between Dietary Knowledge and Food Preferences in Residents Aged 18 and Over in China Based on Latent Class Analysis / 中国医学科学院学报

Objective To investigate the food preferences and explore the potential association between dietary knowledge and food preferences in residents aged 18 and over in China,so as to provide a basis for promoting healthy diets.Methods The latent class analysis was carried out with the 2015 cross-sectional data of China health and nutrition survey to categorize the food preferences among 8 783 residents aged 18 and over.Multinomial Logistic regression was adopted to assess the association between and dietary knowledge and food preferences.Results The food preferences of the residents aged 18 and over in China were classified into preference for less vegetable(3.28%),lack of preference(11.20%),diverse preferences(4.19%),and preference for healthy diets(81.33%).The proportion of the adults with dietary knowledge was 36.87%(3 238/8 783).The dietary knowledge varied in the adults with different food preferences(all P<0.001).After adjusting for gender,age,urban and rural distribution,education background,and annual household income,for each point increase in the dietary knowledge score,there was an estimated reduction of 22% in the probability of preferring less vegetables(OR=0.78,95%CI=0.76-0.80, P<0.001),13% in the probability of lacking preference(OR=0.87,95%CI=0.86-0.89, P<0.001),and 3% in the probability of having diverse preferences(OR=0.97,95%CI=0.94-1.00, P=0.030).Compared with those lacking dietary knowledge,the individuals with dietary knowledge had a 77% less probability of preferring less vegetables(OR=0.23,95%CI=0.16-0.32, P<0.001),a 55% less probability of lacking preference(OR=0.45,95%CI=0.39-0.53, P<0.001),and a 23% less probability of having diverse preferences(OR=0.77,95%CI=0.61-0.96, P=0.023).Conclusions The residents aged 18 and over in China presented four food preferences,including preference for less vegetables,lack of preference,diverse preferences,and preference for healthy diets,the last of which had the highest proportion.The individuals with lower levels of dietary knowledge have higher probability of preferring unhealthy food.

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.

Mechanism of m6A methyltransferase 3 in the pathogenesis of diabetic cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the role and mechanism of N6-methyladenosine(m6A)methyltransferase 3(METTL3)in the pathogenesis of diabetic cataract.METHODS: We cultured SRA01/04 cells in low and high sugar media for 24h and measured changes in epithelial-mesenchymal transition(EMT)indicators(E-Cadherin, N-Cadherin, ZO-1 and α-SMA)using RT-qPCR and Western blot assays. Cell migration was also assessed using transwell and scratch assays. To investigate the expression level and localization of METTL3 in human lens anterior capsules tissues. Additionally, we used m6A dot blot assay to detect the m6A methylation level of cells cultured in low and high glucose media for 24h, and employed RT-qPCR and Western blot experiments to detect RNA and protein expression of METTL3 in cells. We then treated the cells with METTL3 inhibitor and measured changes in EMT markers by RT-qPCR and Western blot; m6A methylation level was detected by m6A dot blot test; cell migration was detected by Transwell. Finally, the expression of transforming growth factor-β(TGFβ1)in cultured cells was assessed by immunofluorescence staining and the expression levels of TGFβ1 and SNAIL in cells were determined using RT-qPCR and Western blot.RESULTS: Under high glucose conditions, the expression of EMT markers, METTL3, and m6A methylation levels were significantly increased in cells(P&#x003C;0.05). Furthermore, the migratory ability of cells was higher in high-sugar medium than in low-sugar medium. In human lens anterior capsules, METTL3 expression was higher in patients with diabetic cataract compared to those with age-related cataract. Importantly, treatment with the METTL3 inhibitor STM2457 inhibited EMT in cells, the expression of TGFβ1 and SNAIL, as well as m6A methylation levels in cells(all P&#x003C;0.05)compared to high-sugar + dimethyl sulfoxide(DMSO)group. Moreover, the migratory capacity of cells was reduced after the addition of STM2457 compared to the high-sugar + DMSO group.CONCLUSION:METTL3 promotes the EMT in human lens epithelial cells under high glucose conditions by activating the TGFβ1/SNAIL pathway, thus contributing to the development of diabetic cataracts.

Methyltransferase-like 3-mediated N6-methyladenosine methylation modification regulates the biological activity of vascular endothelial cells via the Notch pathway / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the role and mechanism of methyltransferase-like 3(METTL3)-mediated N6-methyladenosine(m6A)methylation modification in regulating biological activity of vascular endothelial cells in the pathogenesis of choroidal neovascularization.METHODS: Human umbilical vein endothelial cells(HUVEC)cultured in vitro were divided into the following groups: control group(normal culture), low density lipoprotein(LDL)group, fluorescence-labelled LDL(Dil-LDL)group, 12.5μg/mL and 25μg/mL oxidized LDL(ox-LDL)groups, 12.5μg/mL and 25μg/mL fluorescence-labelled ox-LDL(Dil-ox-LDL)groups, DMSO group, STM2457(METTL3 inhibitor)group, DAPT group; and monkey retina-choroidal endothelial cells(RF/6A)cultured in vitro were divided into control group, DMSO group, 12.5 μg/mL ox-LDL group, and DAPT group. Endocytosed lipoprotein level was examined through fluorescence microscopy. RNA m6A methylation level was detected through a dot blot assay. Protein and RNA levels of METTL3 or angiogenesis-related markers were measured through Western blot assays and real-time quantitative polymerase chain reaction(RT-qPCR), respectively. METTL3 expression and localization were investigated through immunofluorescence. Cell migratory and tube formation capacities were assessed through transwell migration and tube formation assays, respectively.RESULTS: Endocytosed lipoprotein levels in HUVECs exposed to Dil-LDL, 12.5μg/mL and 25μg/mL Dil-ox-LDL groups were significantly higher than those in the control group. 12.5μg/mL and 25μg/mL ox-LDL groups significantly increased m6A methylation(all P&#x003C;0.05), METTL3 protein expression(all P&#x003C;0.01), and cell migration and angiogenesis capacities(all P&#x003C;0.01). METTL3 mRNA level was significantly unregulated in the 12.5μg/mL ox-LDL group(P&#x003C;0.05). In comparison to the DMSO group, the addition of STM2457 caused significant decrease in m6A methylation level(P&#x003C;0.05), expression of VEGF and other angiogenesis-related markers(all P&#x003C;0.05), cell migration and angiogenesis capacities(all P&#x003C;0.01)and the expression of NICD(P&#x003C;0.05). However, there were no significant differences in METTL3 protein and mRNA levels(all P&#x003E;0.05). The expression of VEGF and NICD(all P&#x003C;0.05), as well as the ability of cell migration and angiogenesis of RF/6A, was all significantly decreased in the DAPT group compared to the DMSO group(all P&#x003C;0.01).CONCLUSION: METTL3-mediated m6A methylation modification promotes angiogenesis in vascular endothelial cells via the Notch signaling pathway in the pathogenesis of choroidal neovascularization.

Study on biological behavior of small tumor breast cancer with axillary lymph node metastasis as the first symptom / 中国医师进修杂志

Objective:To explore the biological behavior of small tumor (≤1.0 cm) breast cancer with axillary lymph node metastasis as the first symptom, and to provide a powerful reference for clinical accurate treatment.Methods:The clinical, pathological and follow-up data of 60 breast cancer patients with small tumor and axillary lymph node metastasis as the first symptom admitted to the Second Affiliated Hospital of Harbin Medical University and the Third Affiliated Hospital of Harbin Medical University from 2017 to 2019 were analyzed retrospectively (study group). Meanwhile, non-small tumor with negative lymph node (control group A), non-small tumor with positive lymph node (control group B) and small tumor with negative lymph node (control group C) were included as control groups. Selected estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor-2(Her-2) and Ki67 to compare and analyze the difference between primary lesions and axillary lymph node metastasis, and made a comprehensive analysis with the follow-up data.Results:There were no statistically significant differences in the four indexes in primary lymph nodes and metastatic lymph nodes between the study group and the control group ( P>0.05). The expression of HER-2 in control group B, study group, control group C, control group A showed a decreasing trend. In the study group, there were 19 cases with >3 axillary lymph node metastasis, the positive rate of HER-2 was 11/19, and 37 cases with 3 lymph node metastasis, the positive rate of HER-2 was 21.6%(8/37), the difference was statistically significant ( P<0.05), but there was no significant difference in the expression of ER, PR and Ki67 ( P>0.05). In control group B, there was no significant difference between the groups with >3 axillary lymph node metastasis and 3 groups ( P>0.05). Combined with the follow-up data, in the study group with >3 lymph node metastasis, there were 4 cases with distant metastasis and Ki67 expression rate was 4/4, while there were 13 cases with no distant metastasis and Ki67 expression rate was 5/13, the difference was statistically significant ( P<0.05). Conclusions:The expressions of ER, PR, Her-2 and Ki67 in primary breast cancer including small tumor and axillary lymph node metastasis are consistent. In most cases, the overall condition can be evaluated by biological indicators of primary disease, but some patients do have inconsistencies, which should arouse the attention of clinicians for comprehensive condition evaluation. Her-2 positive expression seems to be related to axillary lymph node metastasis as a whole, especially in small tumor breast cancer with T≤1.0 cm. For patients with axillary lymph node metastasis and invasive ductal carcinoma with primary lesion ≤1.0 cm, the high expression of Ki67 seems to indicate that distant metastasis is more likely to occur in the longer term.

Magnetic resonance imaging of ligaments in the elbow joint: normal anatomy and injuries / 中华全科医师杂志

Objective:To explore the magnetic resonance imaging (MRI)features of the normal anatomy and injuries of ligaments in the elbow joint.Methods:Thirty-eight healthy volunteers (38 sides) and 82 patients with elbow joint injuries were recruited in the Radiology Department of Beijing Jishuitan Hospital from February 2019 to February 2022 and the MRI findings were analyzed. The healthy subjects had no history of trauma, elbow joint ligament injury or pain, and the elbow joint function was normal. Among the 82 patients with elbow joint injuries, 8 cases were confirmed by operation and 74 were confirmed by follow-up. The MRI characteristics of normal anatomy and injuries of the medial collateral ligament and lateral collateral ligament complex of the elbow were compared and analyzed by blind method.Results:The medial collateral ligament and lateral collateral ligament complex in 38 healthy volunteers showed as thin strip low signal on T1-weighted imaging (T1WI) and fat suppression proton density-weighted imaging (PD-FS), and the annular ligament showed as annular linear low signal surrounding the radial head. Among the 82 patients with elbow injuries, in the medial side, there were 6 cases with medial collateral ligament injuries alone, 2 with common flexor tendon injuries alone, and 4 with medial collateral ligament and common flexor tendon injuries; while in the lateral side, there were 9 cases with the lateral collateral ligament complex injuries alone, 21 with common extensor tendon injuries alone, and 31 with the lateral collateral ligament complex and common extensor tendon injuries. In addition, there were 9 cases of medial collateral ligament coupled with lateral collateral ligament complex injuries. Among the 9 cases of combined ligament injuries (5 cases with injuries of the common flexor or extensor tendon), 5 cases were complete tears and 4 cases were partial tears. Among the 10 cases of medial collateral ligament injuries, 9 patients were strain and one was complete tear. Among the 40 cases of lateral collateral ligament complex injuries, 29 patients were strain, 10 were partial tears and one was complete tear. The strained ligament showed as thickened and blurred on T1WI, and the fiber was still continuous; while on PD-FS, the injured ligaments demonstrated as heterogeneously increased signal intensity. Partial tear showed as fiber thickening and partial discontinuity. A complete tear showed that the fiber was discontinuous and retracted with surrounding soft tissue edema.Conclusion:MRI is an accurate method for evaluation of the anatomy and pathological conditions of the medial collateral ligament and lateral collateral ligament complex of the elbow joint, and has important application value in the diagnosis and treatment of elbow ligament injury.

Occurrence and risk factors of anal margin edema after Milligan-Morgan hemorrhoidectomy in patients with mixed hemorrhoids / 中国基层医药

Objective:To investigate the risk factors of anal margin edema after Milligan-Morgan hemorrhoidectomy (MMH) in patients with mixed hemorrhoids.Methods:The clinical data of 600 patients with mixed hemorrhoids undergoing MMH in the First People's Hospital of Wenling from January 2017 to January 2020 were retrospectively analyzed. The patients were divided into study (with anal margin edema, n = 272) and control (without anal margin edema, n = 328) groups according to whether anal margin edema occurred after surgery. Gender, age, surgical incision suture, internal anal sphincter relaxation, infection, intraoperative operation, postoperative defecation, and postoperative fumigation with traditional Chinese medicine were compared. The risk factors of anal margin edema after MMH were analyzed by univariate analysis and logistic regression analysis. Results:There were no significant differences in suture of surgical incision [20.22%(55/272) vs. 18.29% (60/328)], infection [15.44% (42/272) vs. 17.68% (39/328)], internal anal sphincter relaxation [15.81% (43/272) vs. 17.68% (58/328)], and postoperative fumigation with traditional Chinese medicine [72.79% (198/272) vs. 71.65% (235/328)] between the two groups ( χ2 = 0.35, 1.60, 0.37, 0.09, all P > 0.05). Multivariate logistic regression analysis showed that female gender, age ≤ 60 years, unreasonable postoperative operation, and abnormal defecation were all independent risk factors for anal margin edema after MMH ( OR = 2.28, 2.52, 5.95, 3.07, all P < 0.05). Conclusion:Gender, age, surgical operation, and postoperative defecation are the risk factors for anal margin edema after MMH. Clinically, it is necessary to carry out reasonable perioperative intervention to avoid the occurrence of postoperative anal margin edema.

Effects of combined administration of loganin and berberine on bone metabolism in diabetic mice / 中国药理学通报

Aim To investigate the effects of combined administration of loganin and berberine on bone structure and metabolism in diabetic mice and its potential mechanism.Methods The diabetic ICR mouse model was induced by high fat diet(HFD).After 10 weeks of combined intervention, the effects of loganin and berberine on body weight, body fat rate, blood glucose, blood lipid and serum oxidative stress levels were observed.Bone microstructure was scanned by micro-CT.Biomechanical characteristics of bone were measured by three-point bending test, and material properties were detected by fourier transform infrared(FTIR).The pathological changes were observed by HE and TRAP staining.Protein expressions involved in advanced glycation end products(AGEs)and their receptors(RAGE)/nuclear factor-κB(NF-κB)signaling pathway were detected by immunohistochemistry.Results The combined administration of loganin and berberine could significantly inhibit the weight gain, reduce the levels of blood glucose, blood lipid and oxidative stress, as well as improve glucose tolerance.In addition, combined intervention also decreased the expression levels of the proteins involved in AGEs/RAGE/NF-κB signaling pathway, and improved bone microstructure, finally contributing to increasing bone quality in diabetic mice.Conclusions The combination of loganin and berberine could improve bone metabolism in diabetic mice, which may be related to AGEs/RAGE/NF-κB signaling pathway.