AIM:To investigate alterations in the expression levels of inflammatory cytokines and subsets of CD8+ T cells in the peripheral blood of patients with diabetic retinopathy(DR).METHODS:Retrospective study. A total of 40 patients with type 2 diabetes admitted to Xi'an People's Hospital(Xi'an Fourth Hospital)from April to July 2022 were recruited for this study and categorized into two groups: 20 cases in the simple type 2 diabetes mellitus(DM)group, and 20 cases in the DR group. Additionally, 20 healthy individuals undergoing routine physical examinations served as the control group. The expression levels of cytokines, including interleukin(IL)-6, IL-8, and IL-10 in peripheral blood were quantified using ELISA. Flow cytometry was employed to analyze the expression of programmed cell death-1(PD-1), T cell immunoglobulin domain and mucin domain protein-3(TIM-3), CD28, and CD57 on CD8+ T cells.RESULTS:The peripheral blood expression of IL-6, IL-8, and IL-10 inflammatory cytokines were significantly elevated in DR patients as detected by ELISA(all P<0.001); flow cytometry analysis showed that the expression of PD-1, TIM-3, and CD57 were elevated in peripheral blood CD8+ T cells of DR patients(all P<0.001), and the expression of CD28 was decreased(all P<0.001).CONCLUSION:In DR patients, CD8+ T cells may undergo depletion and senescence as a result of elevated pro-inflammatory cytokines, including IL-6, IL-8, and IL-10.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.

Purpose: Drug resistance is one of the main causes of chemotherapy failure in patients with small cell lung cancer (SCLC), and extensive biological studies into chemotherapy drug resistance are required. Materials and Methods: In this study, we performed lncRNA microarray, in vitro functional assays, in vivo models and cDNA microarray to evaluate the impact of lncRNA in SCLC chemoresistance. Results: The results showed that KCNQ1OT1 expression was upregulated in SCLC tissues and was a poor prognostic factor for patients with SCLC. Knockdown of KCNQ1OT1 inhibited cell proliferation, migration, chemoresistance and promoted apoptosis of SCLC cells. Mechanistic investigation showed that KCNQ1OT1 can activate transforming growth factor-β1 mediated epithelial-to-mesenchymal transition in SCLC cells. Conclusion Taken together, our study revealed the role of KCNQ1OT1 in the progression and chemoresistance of SCLC, and suggested KCNQ1OT1 as a potential diagnostic and prognostic biomarker in SCLC clinical management.

Objective:To explore the clinical application values of a nomogram based on preoperative breast MRI and axillary ultrasonography imaging parameters for predicting the risk of sentinel lymph node (SLN) metastasis in early-stage breast cancer patients.Methods:Three hundred and ninty-seven female patients (mean age 48.0±10.7 years old, range 25-81 years old) who admitted to Sun Yat-sen University Cancer Center from May 2007 to December 2017 were enrolled in this study. All patients were diagnosed as primary unilateral invasive early-stage breast cancer confirmed by surgical pathology. Preoperative breast MRI, axillary ultrasonography and clinical pathological data of enrolled patients were retrospectively analyzed. According to the pathological results of sentinel lymph node biopsy (SLNB), the cases were divided into negative SLN group ( n=200) and positive SLN group ( n=197). Clinicopathologic data, MRI and axillary ultrasound features were analyzed and compared between two groups. Logistic regression analysis was used to select independent risk factors. Then a predictive model was constructed and a nomogram was made for visualizing the associations between the predictive factors and SLN metastasis. Goodness-of-fit of the model was evaluated by using the Hosmer-Lemeshow test. Predictive performance was assessed based on the receiver operating characteristic (ROC) curves. Bootstrap resampling was performed for internal validation. Results:Significant differences were found in patient age, lymphovascular invasion status, PR status, HER2 status and molecular subtype between negative and positive SLN groups (all P<0.05); MRI features including tumor size, mass margin, long and short diameter, as well as the ratio of long to short diameter of LNs, LN margin, presence or absence of LN hilum, and axillary LNs symmetry were found significantly different between negative and positive SLN groups (all P<0.05); as for the axillary LN ultrasonography parameters, the interface between cortex and medulla, presence or absence of cortical thickening, and LN hilum were significantly different between negative and positive SLN groups (all P<0.05). Logistic regression analysis results showed that several factors could be identified as predictors of SLN metastasis, including patient age, MRI features (lymph node margin, presence or absence of lymph node hilum, and lymph node symmetry), axillary ultrasonography descriptors (presence or absence of cortical thickening) and pathological factors (lympovascular invasion, PR and HER2 status). The nomogram with patient age and the above imaging factors showed good,prediction performance with the area under the ROC as 0.778. Combining with the pathological parameters, the prediction performance of the nomogram model was significantly improved, yielding the area under the ROC of 0.866. Conclusions:The nomogram based on breast MRI and axillary ultrasonography can be applied as a noninvasive quantitative tool to predict the risk of SLN metastasis in early-stage breast cancer, which may facilitate decision-making for axillary treament strategy preoperatively.

Objective:To explore the feasibility of soft copy image of chest digital radiography (DR SC) in pneumoconiosis diagnosis by observing the reading effect of DR SC and comparing it with high kV film-screen chest radiography (FSR HkV) . To provide a basis for the establishment of a regional information network platform for pneumoconiosis diagnosis. Methods:A total of 119 miners who were exposed to silica dust and engaged in copper or lead-zinc mining were collected by the Third People's Hospital of Yunnan from October 2017 to August 2019. The pulmonary X-ray findings of DRSC and FSR HkV in each case were independently judged and diagnosed by three experienced diagnostic physicians, and the final decision was made according to the consensus of most doctors. The consistency of the two imaging methods was analyzed by observing the main small opacity shape, the overall density, the range of distribution, the aggregation of the small opacity and the big opacity, and the diagnosis stage. Results:there were 118 males and 1 female with an average age of 46.21 years. Average exposure time 7.38 years. The pulmonary X-ray findings of 113 cases with two imaging methods were mainly the round small opacity of p,q and r,but the reticular irregular opacity were not prominent, Only one case of FSR HkV judgment p shape and DR SC judgment q shape were observed, The coincidence rate was 99.12% (112/113) . huger opacity were observed in the other 6 cases. The coincidence rate was 95.51% (4/89) between pneumoconiosis-free and stageⅠ, and there was no significant difference between stageⅡand stage Ⅲ (30/30, P>0.05) . Conclusion:The x-ray findings of Silicosis with small round shadow in lung can be used by DR SC in diagnosis and staging.

Objective:To explore the feasibility of soft copy image of chest digital radiography (DR SC) in pneumoconiosis diagnosis by observing the reading effect of DR SC and comparing it with high kV film-screen chest radiography (FSR HkV) . To provide a basis for the establishment of a regional information network platform for pneumoconiosis diagnosis. Methods:A total of 119 miners who were exposed to silica dust and engaged in copper or lead-zinc mining were collected by the Third People's Hospital of Yunnan from October 2017 to August 2019. The pulmonary X-ray findings of DRSC and FSR HkV in each case were independently judged and diagnosed by three experienced diagnostic physicians, and the final decision was made according to the consensus of most doctors. The consistency of the two imaging methods was analyzed by observing the main small opacity shape, the overall density, the range of distribution, the aggregation of the small opacity and the big opacity, and the diagnosis stage. Results:there were 118 males and 1 female with an average age of 46.21 years. Average exposure time 7.38 years. The pulmonary X-ray findings of 113 cases with two imaging methods were mainly the round small opacity of p,q and r,but the reticular irregular opacity were not prominent, Only one case of FSR HkV judgment p shape and DR SC judgment q shape were observed, The coincidence rate was 99.12% (112/113) . huger opacity were observed in the other 6 cases. The coincidence rate was 95.51% (4/89) between pneumoconiosis-free and stageⅠ, and there was no significant difference between stageⅡand stage Ⅲ (30/30, P>0.05) . Conclusion:The x-ray findings of Silicosis with small round shadow in lung can be used by DR SC in diagnosis and staging.

Objective: To summarize the clinical manifestations and treatment of retinal artery occlusion and cerebral infarction caused by facial injection of hyaluronic acid. Methods: Fifteen cases (15 eyes) with vision lose caused by facial cosmetic injection of hyaluronic acid visited Xi＇an No.4 Hospital from December 2010 to January 2017. The clinical data were collected such as general medical history and treatment methods, and follow-up for 1 year. Results: All patients were female, 22-41 years old, with average age of 33. All patients were injected with hyaluronic acid. For 8 patients the fillers were injected in the forehead, 3 patients were in the glabellar region, 3 patients were in the nasolabial fold, and 1 patient was in the temporal of left eye. All patients had vision lose after injection, the visiting time was 1 to 6 hours. 13 patients were central retinal artery occlusion (CRAO). 1 patient was retinal branch artery occlusion (BRAO), 1 patient was ischemic optic neuropathy (ION), 13 patients manifested as no light perception (NLP), 1 patient was 0.6, 1 patient was CF/30 cm, and 14 patients with cerebral infarction, manifested as headache, dizziness. All patients were given emergency treatment, and 9 patients had treated with interventional thrombolysis therapy. After treatment 11 patients, visual acuity had no significant improvement, but 4 patients improved. Headache, dizziness symptoms disappeared, but cerebral infarction lesions still existed on MRI. Conclusions Human face is a rich blood supply; vision loss and cerebral infarction could occur after injection of hyaluronic acid. After urgent treatment visual acuity is not improved obviously, eventually leading to irreversible visual impairment or even loss.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. METHODS: Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. RESULTS: Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). CONCLUSIONS The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cisplatin ; administration & dosage ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Etoposide ; administration & dosage ; Female ; Humans ; Interleukin Receptor Common gamma Subunit ; deficiency ; genetics ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; pathology ; Transplantation, Heterologous ; methods ; Xenograft Model Antitumor Assays