Objective To observe the effects of repeated intravitreal injections of ranibizumab and aflibercept on cor-neal morphology of patients with neovascular age-related macular degeneration(nAMD),diabetic macular edema(DME)or retinal vein obstruction(RVO).Methods In this prospective study,64 patients(64 eyes)who underwent therapy in the injection center of the Ophthalmology Department of our hospital from June 2021 to June 2022 were enrolled,including 19 nAMD patients,20 DME patients and 25 RVO patients.Among these patients,29 were treated with aflibercept(40 g·L-1)and 35 were treated with ranibizumab(10 g·L-1).Monocular injections were adopted for all patients,and 3+pro re nata(PRN)therapy was used.Confocal microscope was used for corneal nerve examination,and corneal endo-thelial microscope was used to measure corneal thickness(CT)and corneal endothelial cells.The CT,corneal endothelial cell density(ECD),coefficient of variation(CV),average cell size(ACS),proportion of hexagonal cells(Hex％),cor-neal nerve fiber length(CNFL),corneal nerve fiber density(CNFD)of patients with nAMD,DME and RVO after repeated intravitreal injections of anti-vascular endothelial growth factor(VEGF)drugs were compared,and those parameters at 1 month after injection of different anti-VEGF drugs were compared with the baseline.Results Before injection,ECD in the DME group was lower than that in the nAMD and RVO groups,and the ACS in the DME group was higher than that in the nAMD and RVO groups(all P＜0.05).There was no significant difference in the other indexes among the three groups(all P＞0.05).After 3 injections of anti-VEGF drugs,the ECD in the DME group was lower than that in the nAMD and RVO groups,the ACS in the DME group was higher than that in the nAMD and RVO groups,and the CNFL in the DME group was lower than that in the nAMD and RVO groups(all P＜0.05).The ECD decreased compared with that before injection from the 2nd injection of aflibercept in the nAMD group(all P＜0.05).Hex％decreased significantly after each injection compared with the baseline(all P＜0.05).Other indexes have no significant differences from the baseline(all P＞0.05).In the RVO group,ECD decreased from the 2nd ranibizumab injection compared with the baseline(all P＜0.05).Conclu-sion Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex％and ECD to a certain extent.After injec-tions,CNFL in the DME group is significantly lower than that in the nAMD and RVO groups.

Objective:To assess the accuracy of two-dimensional (2D) photographs in measuring esthetic parameters of the maxillary anterior teeth by comparing them with measurements obtained from three-dimensional (3D) dental models.Methods:A total of one hundred volunteers (49 males, 51 females, aged 18-23 years) were recruited from School and Hospital of Stomatology, Wuhan University from January to February 2024. 3D digital models of their dentitions were obtained using an intraoral scanner, and standardized frontal 2D intraoral photographs were captured with a digital camera. The lengths, widths and width/length ratio of the bilateral incisors, lateral incisors and canines were measured on both the 3D digital models and the 2D intraoral photographs. The width ratios of adjacent maxillary anterior were also calculated on the 2D intraoral photographs and the frontal view of 3D digital models.Results:The widths of lateral incisors [(5.85±0.60) mm] and canines [(4.73±0.71) mm] and the lengths of canines [(8.72±0.96) mm] in the 2D intraoral photographs were significantly lower than those in 3D digital models [(6.65±0.59), (7.76±0.60), (8.90±0.86) mm] ( t=-18.24, P<0.001; t=-54.43, P<0.001; t=-4.40, P<0.001), while there were no significant differences in the lengths and widths of the other teeth ( P>0.05). The width/length ratios measured from the 2D intraoral photographs for the lateral incisors and canines (0.74±0.08, 0.55±0.08) were significantly lower than those measured in the 3D digital models (0.84±0.09, 0.88±0.09) ( t=-19.68, P<0.001; t=-50.21, P<0.001), and the width/length ratio of the central incisors showed no significant difference between the two groups ( P>0.05). The width ratios of canines/lateral incisors and lateral incisors/central incisors measured on the 2D intraoral photographs (0.72±0.06, 0.85±0.11) were significantly smaller than those measured in the frontal view of 3D digital models (0.75±0.06, 0.89±0.11) ( t=-9.31, P<0.001; t=-6.58, P<0.001). Conclusions:There is a difference between 2D and 3D measurement results of teeth in the esthetic area and the magnitude of the difference varies with their position in the dental arch. When analyzing the measurement of the anterior teeth, it is necessary to choose the appropriate method according to the target tooth position.

As the final resolution for end-stage lung disease, lung transplantation can not only significantly prolong the survival, but also remarkably improve the quality of life of recipients. In recent decades, with the advancement of surgical techniques, immunosuppressants and post-transplantation management, the quantity of lung transplantation has been surged around the globe. However, the shortage of donor lung has severely restricted the development of lung transplantation. It is necessary to develop innovative approaches to expand the donor pool. The number of donors and effective preservation and functional maintenance of potential donor lungs play a key role in expanding the donor pool. The quality of donor lung is a critical precondition to ensure the long-term survival of lung transplant recipients. Preservation and functional maintenance of donor lung are of significance for guaranteeing the quality of lung allograft. In this article, research progresses on the management and maintenance of donor lung before procurement, the procurement of donor lung and the preservation and functional maintenance of lung allograft were reviewed, aiming to provide reference for the development of lung transplantation in clinical practice.

ObjectiveTo evaluate the clinical safety of Naoxintong （NXT） capsules after marketing， find out the potential risk factors of the drug as soon as possible， and reveal the incidence， nature， and clinical manifestations of the adverse events （ADE） and adverse reactions （ADR） of NXT capsules， so as to provide a basis for safe use of the drug in clinical practice. MethodA prospective， large-sample， multi-center observational cohort study was conducted to monitor all the 7 345 inpatients and outpatients orally taking NXT in 14 hospitals in China from January to December in 2018， with at least one follow-up. The demographic characteristics， disease type， NXT medication， ADR occurrence， characteristics， and prognosis of the patients were collected. SPSS 23.0 was used for single-factor and multivariate logistic regression to predict the influencing factors of ADR. ResultThe male and female patients accounted for similar proportions. There were 5 081 patients （79.40%） aged ≥60 years and 3 153 patients （49.27%） with body mass index （BMI） exceeding the normal standard. There were 344 （5.38%） patients with a history of allergy to medicines and food， 9 （0.14%） patients with a family history of allergy， and 52 （0.81%） patients with a history of allergic diseases. The ADRs associated with NXT occurred in 22 patients， with the incidence of 0.34%. The clinical manifestations of ADR appeared in 31 cases， involving 10 organs/systems， of which gastrointestinal system damage was the most common （17， 54.84%）. All ADRs were mild or moderate. Most ADRs （19， 86.36%） occurred within 4 weeks after administration. The patients with alleviated NXT-associated ADRs accounted for 81.82%. No indicators related to significant increases in ADR risks were found. ConclusionNXT is well tolerated in the general population. The hospital centralized monitoring for the clinical safety of oral Chinese patent drugs based on HIS data and Web tracking and follow-up system is an essential means for the post-market research on the safety of drugs.

Objective:To investigate the effects of transepithelial photorefractive keratectomy (TransPRK) and femtosecond small incision lenticule extraction (SMILE) on corneal biomechanics measured by the Ocular Response Analyzer in the early postoperative period.Methods:A cohort study was conducted.The right eyes of 56 patients who underwent TransPRK and 52 patients who underwent SMILE in Dalian Medical University Affiliated Dalian Third People's Hospital from November 2020 to June 2021 were continuously included.The postoperative follow-up was 3 months.The central corneal thickness (CCT) and keratometry (Km) were measured 1 month and 3 months after surgery.The corneal-compensated intraocular pressure (IOPcc), corneal resistance factor (CRF), corneal hysteresis (CH), and 19 repeatable mechanical infrared signal waveform parameters measured by the Ocular Response Analyzer were recorded before the surgery, 1 month and 3 months after the surgery, respectively.The measurement indexs at different time points between two groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Dalian Medical University Affiliated Dalian Third People's Hospital (No.2019-KT-010). Written informed consent was obtained from each patient before surgery.Results:There was no significant difference in CCT, Km, and IOPcc between the two groups at 1 month and 3 months after the surgery (all at P>0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1, dive2 and mslew1 were decreased, while path1, path2, path11, and aplhf were increased at 1 month after the surgery compared with before surgery, showing statistically significant differences (all at P<0.05). In both groups, CRF, CH, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h1, h2, h11, h21, dive1 decreased, while path1, path2, path11, and aplhf were increased at 3 months after the surgery in comparison with before surgery, showing statistically significant differences (all at P<0.05). In SMILE group, the dive2 were decreased at 3 months after the surgery compared with before surgery, and the difference was statistically significant ( P<0.01). At 1 month after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, dive1 and dive2 were higher, while CH, path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). At 3 months after the surgery, p1area, p2area, p1area1, p2area1, w1, w2, w11, w21, h2, h21, dive1 and dive2 were higher, while path1, path2, and path11 were smaller in TransPRK group than in SMILE group, showing statistically significant differences between them (all at P<0.05). Conclusions:Corneal biomechanics are weakened after both TransPRK and SMILE.In the early postoperative period, the mechanical infrared waveform parameters measured by the Ocular Response Analyzer are better after TransPRK than after SMILE.

Objective:To explore the spatial autocorrelation and macro influencing factors of stroke mortality in Zhejiang Province in 2015-2020 and provide a scientific basis for stroke prevention and control strategy.Methods:The data on stroke death were obtained from Zhejiang Chronic Disease Surveillance System. The spatial distribution of stroke mortality was explored by mapping and spatial autocorrelation analysis. The spatial panel model analyzed the correlation between stroke mortality and socioeconomic and healthcare factors.Results:From 2015 to 2020, the average stroke mortality was 68.38/100 thousand. The standard mortality of stroke was high in the areas of east and low in the west, high in the south and low in the north. Moreover, positive spatial autocorrelation was observed (Moran's I=0.274-0.390, P<0.001). Standard mortality of stroke was negatively associated with per capita gross domestic product (GDP) ( β=-0.370, P<0.001), per capita health expenditure ( β=-0.116, P=0.021), number of beds per thousand population ( β=-0.161, P=0.030). Standard mortality of ischemic stroke was negatively associated with per capita GDP ( β=-0.310, P=0.002) and standard management rate of hypertension ( β=-0.462, P=0.011). Standard mortality of hemorrhagic stroke was negatively associated with per capita GDP ( β=-0.481, P<0.001), per capita health expenditure ( β=-0.184, P=0.001), number of beds per thousand population ( β=-0.288, P=0.001) and standard management rate of hypertension ( β=-0.336, P=0.029). Conclusions:A positive spatial correlation existed between stroke mortality in Zhejiang Province in 2015-2020. We must focus more on preventing and controlling strokes in relatively backward economic areas. Moreover, to reduce the mortality of stroke, increasing the investment of government medical and health funds, optimizing the allocation of medical resources, and improving the standard management rate of hypertension are important measures.

Objective To investigate the effect of carrimycin on the biological function of pancreatic cancer cells. Methods Pancreatic cancer cell lines MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 were treated with carrimycin at concentrations of 0 (control group), 2, 4, 8, and 16 μmol/L for 24, 48, and 72 hours. MTT assay was used to measure cell viability; EdU cell proliferation assay was used to observe the effect of carrimycin on DNA replication of pancreatic cancer cells; colony formation assay was used to observe the effect of carrimycin on the proliferation of pancreatic cancer cells; flow cytometry was used to analyze the effect of carrimycin on the cell cycle of pancreatic cancer cells; wound healing assay was used to analyze the effect of carrimycin on the migration of pancreatic cancer cells; Western blot was used to measure the expression levels of the markers such as epithelial-mesenchymal transition (EMT) and cell cycle-dependent protein kinase inhibitor 1A (P21); immunofluorescence assay were used to measure the expression levels of EMT-related markers. An analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the control group, carrimycin significantly inhibited the proliferative activity of MIA PaCa-2, BxPC-3, Panc-1, and PATU 8988 cells in a concentration- and time-dependent manner (all P < 0.01); carrimycin at concentrations of 4, 8, and 16 μmol/L significantly reduced DNA replication in MIA PaCa-2 cells ( t =2.378, 4.984, and 18.970, all P < 0.05) and BxPC-3 cells ( t =4.879, 6.089, and 9.521, all P < 0.01); after treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, colony formation ability significantly decreased with the increase in drug concentration in MIA PaCa-2 cells ( t =5.889, 11.240, and 15.840, all P < 0.001) and BxPC-3 cells ( t =6.717, 15.800, and 18.850, all P < 0.001). After treatment with carrimycin at concentrations of 4, 8, and 16 μmol/L, there was a significant increase in the proportion of cells in G1 phase in MIA PaCa-2 cells ( t =9.071, 12.280, and 19.360, all P < 0.0001) and BxPC-3 cells ( t =3.061, 4.962, and 8.868, all P < 0.05), and there was a significant reduction in the proportion of cells in S phase in MIA PaCa-2 cells ( t =2.316, 4.165, and 5.562, all P < 0.05) and BxPC-3 cells ( t =2.424, 3.264, and 5.744, all P < 0.05). Western blot further demonstrated that compared with the control group, the expression level of the cell cycle-related protein P21 gradually increased with the increase in the concentration of carrimycin in MIA PaCa-2 cells ( t =5.437, 6.453, and 8.799, all P < 0.001) and BxPC-3 cells ( t =25.130, 44.750, and 52.960, all P < 0.000 1). Wound healing assay showed that after treatment for 12, 24, and 48 hours, carrimycin at concentrations of 0, 4, 8, and 16 μmol/L significantly reduced the lateral migration of MIA PaCa-2 cells (all P < 0.05) and BxPC-3 cells (all P < 0.05). Western blot showed that compared with the control group, carrimycin treatment at concentrations of 4, 8, and 16 μmol/L significantly upregulated the expression of the epithelial marker E-cadherin in MIA PaCa-2 cells ( t =2.388, 4.899, and 5.819, all P < 0.05) and BxPC-3 cells ( t =2.533, 5.836, and 6.774, all P < 0.05) and significantly downregulated the expression of the interstitial marker Snail in MIA PaCa-2 cells ( t =12.440, 14.830, and 16.800, all P < 0.000 1) and BxPC-3 cells ( t=5.039, 5.893, and 7.725, all P < 0.01), and it also significantly downregulated the expression of the interstitial marker Vimentin in MIA PaCa-2 cells ( t =3.105, 7.752, and 11.200, all P < 0.05) and BxPC-3 cells ( t =2.555, 4.883, and 9.153, all P < 0.05). Conclusion Carrimycin can effectively inhibit the proliferation, migration, and EMT process of pancreatic cancer cells, thereby exerting an antitumor biological activity.

Objective:To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated.Methods:This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tc m -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results:Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) ( P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI ( P = 0.04) or US ( P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions:4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.

Objective: To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) . Methods: Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH. Results: Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup. Conclusion DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.

Objective:To evaluate the correlation of community management index of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases.Methods:From 2016 to 2018, the management of essential hypertension and type 2 diabetes were obtained from annual report of comprehensive prevention and control of chronic diseases in communities of Zhejiang province. The death data of chronic diseases were obtained from Information Management System of Chronic Diseases of Zhejiang province and annual population data were obtained from Public Security Bureau of Zhejiang Province. The management of essential hypertension and type 2 diabetes in communities of Zhejiang Province from 2016 to 2018 was described. The death status of major chronic diseases, including cardiovascular diseases, malignant tumors, diabetes and chronic respiratory diseases, in the same period was also described. Spearman correlation analysis and linear regression model were used to explore the correlation of community management of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases.Results:The number of essential hypertension patients under standardized management, blood pressure control and regular medication increased from 3.127 3, 2.811 5 and 3.569 7 million in 2016 to 3.355 9, 3.151 8 and 4.010 6 million in 2018, respectively. The number of type 2 diabetes patients with standardized management, blood glucose control and regular medication increased from 0.805 5, 0.687 5 and 0.913 4 million in 2016 to 0.912 6, 0.798 7 and 1.064 8 million in 2018, respectively. The standardized mortality rate of chronic diseases decreased from 403.07/100 000 in 2016 to 380.07/100 000 in 2018. The proportion of premature deaths of chronic diseases decreased from 28.39% in 2016 to 26.90% in 2018. The proportion of deaths from major chronic diseases in all chronic diseases decreased from 90.96% in 2016 to 90.69% in 2018.The probability of premature mortality decreased from 10.68% in 2016 to 9.67% in 2018. The spearman correlation analysis showed that the blood pressure control and regular drug use were negatively correlated with the probability of premature death of major chronic diseases ( r values were -0.367 and -0.392; P values were 0.035 and 0.024). According to the linear regression model analysis, with increase of 100 000 of essential hypertension control cases or regular medication use cases of type 2 diabetes, the probability of premature death of major chronic diseases decreased by 0.47% (95% CI: 0.39%, 0.54%) or 1.31% (95% CI: 1.12%, 1.50%), respectively. Conclusion:From 2016 to 2018, the community management of essential hypertension and type 2 diabetes was negatively correlated with probability of premature death of major chronic diseases in Zhejiang province.