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.

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.

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.

China guideline for the screening and early detection of prostate cancer (2022, Beijing) / 中华肿瘤杂志

Prostate cancer (PC) is one of the malignant tumors of the genitourinary system that occurs more often in elderly men. Screening, early diagnosis, and treatment of the PC high risk population are essential to improve the cure rate of PC. The development of the guideline for PC screening and early detection in line with epidemic characteristics of PC in China will greatly promote the homogeneity and quality of PC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. This guideline strictly followed the World Health Organization Handbook for Guideline Development and combined the most up-to-date evidence of PC screening, China's national conditions, and practical experience in cancer screening. A total of fifteen detailed evidence-based recommendations were provided with respect to the screening population, technology, procedure management, and quality control in the process of PC screening. This guideline aimed to standardize the practice of PC screening and improve the effectiveness and efficiency of PC prevention and control in China.

Kimura disease with renal impairment: case series and literature review / 中华肾脏病杂志

Objective:To analyze the clinical and pathological characteristics, treatment and prognosis of renal changes in patients with Kimura disease and improve the clinicians′ understanding on renal manifestations of Kimura disease.Methods:The clinical data of Kimura disease patients with definite diagnosis and detailed data in Peking Union Medical College Hospital from January 1980 to August 2020 were retrospectively analyzed. The patients were divided into renal impairment group and non-renal impairment group according to whether the kidney was involved or not and the related clinical data between the two groups were compared. The patients presenting with nephrotic syndrome were followed up.Results:There were 60 patients with Kimura disease confirmed by pathological diagnosis with 48 males. The median age was 33(3, 62) years old, and the median duration was 36(12, 111) months. There were 18 cases complicated with renal injury in 49 patients with complete routine urine and renal function examination and the main manifestations of renal injury were proteinuria and/or microscopic hematuria. There was no significant difference at age, sex and absolute value of eosinophils between the two groups (all P>0.05). Compared with the renal inpairment group, patients in non-renal inpairment group had longer course of disease, higher levels of hypersensitive C-reactive protein and erythrocyte sedimentation rate, and lower median values of total eosinophils and total IgE, but there was no statistically significant difference (all P>0.05). Among the patients with renal involvement, 6 patients met the diagnostic criteria for nephrotic syndrome, and 5 of them completed renal biopsies. The renal pathological diagnosis was membranous nephropathy in 2 cases and minimal change disease in 3 cases, and no interstitial eosinophil infiltration was found in renal biopsy tissues. These patients had a good response to glucocorticoids and/or immunosuppressive therapy, and achieved complete remission of nephrotic syndrome; at the same time, lymphadenopathy caused by Kimura disease could be well controlled. Conclusions:Kimura disease can combine with various renal lesions, and the pathology of nephrotic syndrome can be membranous nephropathy or minimal change nephropathy. After energetic treatment of glucocorticoids and/or immunosuppressive therapy, nephrotic syndrome can be completely relieved, and lymphadenopathy can be well controlled. The relationship between Kimura disease and renal disease needs further study.

MRI manifestations of anatomy and injuries of thumb extensor and flexor mechanism / 中华全科医师杂志

Objective:To explore the anatomy and injuries features of the thumb extensor and flexor mechanism with MRI.Methods:Ten healthy subjects without thumb injury and 20 patients with thumb extensor or flexor mechanism injuries were recruited in the study between September 2013 and September 2021. All subjects underwent MRI examination, the MRI features of thumb extensor or flexor mechanism in healthy subjects and patients were analyzed. The imaging findings were compared with the surgical results and confirmed by followed up in patients.Results:The healthy subjects showed homogeneous low-signal-intensity on T1-weighted and proton-fat saturation sequence(PD FS) images. Twenty patients with thumb extensor or flexor mechanism injures(including 8 cases of extensor pollicislongusinjury,1 case of extensor pollicisbrevis injury, 4 cases of flexor pollicislongus injury, 2 cases offlexor pollicis brevis injury and 5casesofpulley injury) demonstrated poor definition in T1WI, and heterogeneously increased signal intensity in PD-FS. Depending on the degree of injury, the fibers may be partially or completely discontinuity of the involved tendons. There was edema in the soft tissues surrounding the injured sites.Conclusion:MRI is an accurate method for evaluation of the anatomy and pathological conditions of the thumb extensor and flexor mechanism.

Correlation between distal radioulnar joint effusion and the integrity of triangular fibrocartilage in healthy young adults / 中华全科医师杂志

Objective:To study the relationship between distal radioulnar joint (DRUJ) effusion and the integrity of triangular fibrcarotilage (TFC) in asymptomatic young adults.Methods:Thirty two asymptomatic young adults, 22 males and 10 females with a mean age of 25 year(20-30) were recruited in the study between September 2014 and October 2019. All subjects had no wrist pain, no wrist deformity or wrist mass, and had no history of wrist trauma or surgery. The DRUJ effusion was definedasfluid-like high signal intensityon fatsuppression proton density-weighted MRI.The presence of distal radioulnar joint effusion, the shape of the effusion, and the presence of triangular fibrocartilage abnormalities were documented.Results:Among 32 subjects, 25(78.1%, 15 males and 10 females) presented with distal radioulnar joint effusion on wrist MR images, including linear/tubular in 21 cases(84.0%) and saccular in 4 cases(16.0%).Twenty cases (62.5%) had distal radioulnar joint effusion while the TFC was intact, among whom, the effusion was confined to the proximal side of distal radioulnar jointin 17 cases, and reached the lower surface of TFC in 3 cases. In 5 cases (15.6%) with TFC tear, the effusion reached the lower surface of TFC in 4 cases. There were neutral, positive and negative variations of the ulna in 23, 6 and 3 cases, respectively, among whomthe distal radioulnar effusion was presented in 17, 5, 3 cases, and TFC tear in 1, 4 and 0 cases, respectively.The presence of distal radioulnar effusion was not significantly correlated with genders( P=0.069) or types of ulna variance( P=0.702). Conclusion:The distal radioulnar joint effusion maybe resent in asymptomatic young adults, and it maybe complicated with TFC tear.

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.

Effectiveness of different screening strategies for type 2 diabete on preventing cardiovascular diseases in a community-based Chinese population using a decision-analytic Markov model / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness of different screening strategies for type 2 diabetes to prevent cardiovascular disease in a community-based Chinese population from economically developed areas based on the Chinese electronic health records research in Yinzhou (CHERRY) study.@*METHODS@#A Markov model was used to simulate different systematic diabetes screening strategies, including: (1) screening among Chinese adults aged 40-70 years recommended by the 2020 Chinese Guideline for the prevention and Treatment of Type 2 Diabetes (Strategy 1); (2) screening among Chinese adults aged 35 to 70 years recommended by the 2022 American Diabetes Association Standard of Medical Care in Diabetes (Strategy 2); and (3) screening among Chinese adults aged 35-70 years with overweight or obesity recommended by the 2021 United States Preventive Services Task Force Recommendation Statement on Screening for Prediabetes and Type 2 Diabetes (Strategy 3). According to the guidelines, individuals who were screened positively (fasting plasma glucose ≥ 7.0 mmol/L) would be introduced to intensive glycemic targets management (glycated hemoglobin < 7.0%).The Markov model simulated different screening scenarios for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Number of cardiovascular disease events or deaths could be prevented and number needed to screen (NNS) were calculated to compare the effectiveness of the different strategies. One-way sensitivity analysis on the sensitivity of screening methods and probabilistic sensitivity analysis on uncertainties of diabetes incidence, the sensitivity of screening methods, and intensive glycemic management effects were conducted.@*RESULTS@#Totally 289 245 Chinese adults aged 35-70 years without cardiovascular diseases or diagnosed diabetes at baseline were enrolled. In terms of the number of cardiovascular disease events could be prevented, Strategy 1 for systematic diabetes screening among the adults aged 35-70 years was 222 (95%UI: 180-264), Strategy 2 for systematic diabetes screening among the adults aged 40-70 years was 227 (95%UI: 185-271), and Strategy 3 for systematic diabetes screening among the adults aged 35-70 years with obesity or overweight (body mass index ≥ 24 kg/m2) was 131 (95%UI: 98-164), compared with opportunistic screening. NNS per cardiovascular disease event for the strategies 1, 2 and 3 were 1 184 (95%UI: 994-1 456), 1 274 (95%UI: 1 067-1 564) and 814 (95%UI: 649-1 091), respectively. Compared with Strategy 1, NNS per cardiovascular disease event for Strategy 2 increased by 90 (95%UI: -197-381) with similar effectiveness of cardiovascular prevention; however, NNS per cardiovascular disease event for Strategy 3 was reduced by 460 (95%UI: 185-724) in contrast to the Strategy 2, suggesting that the Strategy 3 was more efficient. The results were consistent in multiple sensitivity analyses.@*CONCLUSION@#Systematic screening for diabetes based on the latest guidelines in economically developed areas of China can reduce cardiovascular events and deaths. However, merely lowering the starting age of screening from 40 to 35 years seems ineffective for preventing cardiovascular disease, while screening strategy for Chinese adults aged 35-70 years with overweight or obesity is recommended to improve efficiency.

Cloning and subcellular location of the PnMYB1R1 gene from Panax notoginseng and expression analysis with different stresses / 药学学报

MYB transcription factors, one of the largest transcription factor families in plants, play an important role in signal transduction, plant growth and plant resistance. In this study a full-length cDNA of the PnMYB1R1 gene was cloned from Panax notoginseng. Sequence analysis, prokaryotic expression and purification, subcellular location, transcriptional activity analysis, tissue-specific analysis and expression analysis under different abiotic stresses was performed. The open reading frame (ORF) of PnMYB1R gene was 738 bp, encoding a protein of 245 amino acids with a predicted molecular mass (MW) of 27.0 kD. The sequence analysis and polygenetic analysis indicated that the PnMYB1R1 protein contains a conserved R3 domain, belonging to TRF-like protein in 1R-MYB-type transcription factors. The recombinant PnMYB1R1 protein was expressed in Escherichia coli BL21(DE3) cells using the prokaryotic expression vector pET28a-PnMYB1R1 and was purified. Subcellular localization analysis showed that PnMYB1R1 was localized in the nucleus. Transcriptional activity analysis indicated that the PnMYB1R1 transcription factor has transcriptional activation activity. Expression analysis indicated that PnMYB1R1 was primarily expressed in roots, followed by stems and leaves, and then rootlets. The expression level of PnMYB1R1 in root, stems, leaves and rootlets was influenced by salt, low temperature and drought treatment, while the abundance of PnMYB1R1 was significantly induced by salt stress in these tissues. These results provide valuable insights into the role of 1R-MYB transcription factors in plant defense.

Apalutamide for patients with metastatic castrationsensitive prostate cancer in East Asia: a subgroup analysis of the TITAN trial / 亚洲男科学杂志(英文版)

Ethnicity might be associated with treatment outcomes in advanced prostate cancer. This study aimed to evaluate the efficacy and safety of androgen deprivation therapy (ADT) combined with apalutamide in East Asians with metastatic castration-sensitive prostate cancer (mCSPC). The original phase 3 Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) trial was conducted at 260 sites in 23 countries. This subgroup analysis included patients enrolled in 62 participating centers in China, Japan, and Korea. Radiographic progression-free survival (PFS), time to prostate-specific antigen (PSA) progression, and PSA changes from baseline were compared between groups in the East Asian population. The intent-to-treat East Asian population included 111 and 110 participants in the apalutamide and placebo groups, respectively. The 24-month radiographic PFS rates were 76.1% and 52.3% in the apalutamide and placebo groups, respectively (apalutamide vs placebo: hazard ratio [HR] = 0.506; 95% confidence interval [CI], 0.302-0.849; P = 0.009). Median time to PSA progression was more favorable with apalutamide than placebo (HR = 0.210; 95% CI, 0.124-0.357; P < 0.001). Median maximum percentages of PSA decline from baseline were 99.0% and 73.9% in the apalutamide and placebo groups, respectively. The most common adverse event (AE) was rash in the apalutamide group, with a higher rate than that in the placebo group (37.3% vs 9.1%). The most common grade 3 or 4 AEs were rash (12 [10.9%]) and hypertension (12 [10.9%]) for apalutamide. The efficacy and safety of apalutamide in the East Asian subgroup of the TITAN trial are consistent with the global results.

Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer / 亚洲男科学杂志(英文版)

The purpose of our study is to investigate the prognostic value of phosphatase and tensin homolog on chromosome 10 (PTEN) expression in patients with de novo metastatic castration naïve prostate cancer (mCNPC). A total of 205 patients with mCNPC at Fudan University Shanghai Cancer Center (Shanghai, China) were retrospectively examined. Immunohistochemical staining of PTEN was performed on prostate biopsy samples of these patients. Associations among clinicopathological features, patient survival and PTEN protein expression were analyzed. PTEN loss occurred in 58 of 205 (28.3%) patients. Loss of PTEN was significantly correlated with high metastatic volume (P = 0.017). No association between PTEN expression and Gleason score was observed. Patients with PTEN loss had significantly shorter progression-free survival (PFS, P < 0.001) and overall survival (OS, P < 0.001) compared with patients with intact PTEN expression. Multivariate analysis showed that elevated alkaline phosphatase, high metastatic volume and PTEN loss were independent poor prognostic factors for PFS. The Eastern Cooperative Oncology Group performance status (ECOG PS)#8805; 2 and PTEN loss were independent poor prognostic factors for OS. The adjusted hazard ratio of PTEN loss for PFS and OS was 1.67 (95% confidence interval [CI]: 1.14-2.43, P = 0.008) and 1.95 (95% CI: 1.23-3.10, P = 0.005), respectively. PTEN loss was also significantly associated with shorter PFS (P = 0.025) and OS (P < 0.001) in patients with low-volume metastatic disease. Our data showed that PTEN loss is an independent predictor for shorter PFS and OS in patients with de novo mCNPC.

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.

Fundus changes presented by OCT and OCTA after scleral buckling for rhegmatogenous retinal detachment / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the changes of the morphology and structure of macula, blood flow density of macula and optic disc, as well as retinal nerve fiber layer thickness by optical coherence tomography(OCT)and optical coherence tomography angiography(OCTA)in patients with rhegmatogenous retinal detachment(RRD)under went sclera buckling(SB). METHODS: As a cross-sectional case-controlled study, 25 patients(25 eyes)were diagnosed with RRD in the department of ophthalmology, Ganzhou People's Hospital from July 2014 to March 2021. The differences in the vascular density(VD)of superficial vessel cluster(SVC), the VD of deep vessel cluster(DVC)of macula, the SVC-VD of optic disc, retinal nerve fiber layer(RNFL), central macular thickness(CMT), subfoveal choroidal thickness(SFCT)and outer structure of macula between the affected eyes and healthy eyes at the last post-operative follow-up were compared, and the correlation indicators affecting best corrected visual acuity(BCVA, LogMAR)of the affected eyes at the last follow-up were analyzed. RESULTS: There were no statistically significant in SVC-VD and DVC-VD of macula, SVC-VD of optic disc, RNFL, CMT, SFCT between the affected eyes and healthy eyes at the last post-operative follow-up(all P&#x003E;0.05); At the last follow-up visit, the comparison of macular outer structure on OCT between the affected eyes and the healthy eyes showed that the light band integrity of the external limiting membrane(ELM), myoid zone(MZ), ellipsoid zone(EZ)and outer segment of photoreceptor(OS)had no statistically significant difference(all P&#x003E;0.05), while the light band integrity of interdigitation zone(IZ)had significant difference(P=0.014); The difference of BCVA(LogMAR)between the affected eyes and the healthy eyes at the last follow-up was statistically significant(P=0.002). There was significant correlation between BCVA(LogMAR)of affected eyes at the last post-operative follow-up and the presence or absence of macular involvement, the correlated with SVC-VD of optic disc, the integrity of the light bands of ELM, MZ, EZ, OS and IZ on the outer structure of macula, it was positively correlated with the presence or absence of macular involvement(rs=0.401, P=0.047)and it was negatively correlated with SVC-VD of optic disc, the integrity of the light bands of ELM, MZ, EZ, OS and IZ on the outer structure of macula(all P&#x003C;0.05).CONCLUSION: The OCT and OCTA can be used to observe fundus changes after SB surgery for RRD to obtain long-term follow-up information related to vision prognosis, and visual prognosis depends on the recovery of retinal outer structure, and the integrity of IZ structure is more important for visual recovery; The SVC-VD of optic disc is correlated with visual prognosis, and whether it was correlated with intraocular pressure require further observation and verification with postoperative continuous data.