Characterization of circRNA expression profiles associated with non-Mendelian inheritance in feather growth of chickens.

1. Non-coding RNAs, such as miRNAs, play a crucial role in chicken feather growth rate. However, circular RNA (circRNA) expression profiles in fast- and slow-feathering chickens that follow and do not follow Mendelian inheritance are unclear.2. The circRNA expression profiles was analysed by RNA sequencing of hair follicles of slow-feathering chickens that follow genetic rules and fast-feathering chickens that did not follow genetic rules. Differentially expressed circRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was then constructed and the key factors and regulation mechanisms controlling feather growth rate were identified.3. The results revealed that 67 circRNAs were significantly differentially expressed in hens, including 22 up-regulated and 45 down-regulated circRNAs in non-Mendelian inheritance-mediated fast-feathering hens compared with Mendelian inheritance-mediated slow-feathering hens. In addition, 16 significantly differentially expressed circRNAs were identified in cockerels, including nine up-regulated and seven down-regulated circRNAs in non-Mendelian inheritance-mediated fast- compared with Mendelian inheritance-mediated slow-feathering cocks. Moreover, circRNA-mediated ceRNA regulation of hair follicle formation was particularly abundant in the Jak-STAT, Wnt and Toll-like receptor signalling pathways. Furthermore, circABI3BP was seen to be a crucial circRNA in regulating feather growth rate, by binding with gga-miR-1649-5p to regulate SSTR2 expression.4. In conclusion, this study analysed circRNA expression profiles in fast- and slow-feathering chickens that follow and do not follow Mendelian inheritance, which laid the foundation for understanding the role of circRNA in chicken feather growth rate.

Differences in aqueous humor protein profiles in patients with proliferative diabetic retinopathy before and after aflibercept treatment.

PURPOSE: To investigate the changes in aqueous humor (AH) protein profiles before and after intravitreal aflibercept (IVA) treatment in patients with proliferative diabetic retinopathy (PDR). METHODS: 5 PDR patients provided 10 samples of AH before and after IVA treatment (pre-group vs. post-group). Proteins were identified using liquid chromatography-tandem mass spectrometry. Then, bioinformatics was employed to investigate the functional significance of differentially expressed proteins (DEPs) and hub proteins. RESULTS: A total of 16 DEPs were identified, consisting of 8 downregulated proteins and 8 upregulated proteins. Bioinformatics analysis indicated that the most significantly enriched biological process was "blood coagulation, intrinsic pathway." The most significantly enriched signaling pathway was "complement and coagulation cascades." HBB, HPX, VEGFA, and CA1 were identified as hub proteins for IVA treatment. CONCLUSIONS: Together with the downregulation of the intravitreal vascular endothelial growth factor level, IVA may also change the AH protein composition in PDR patients, with DEPs involved in the blood coagulation, intrinsic pathway, complement, and coagulation cascades. IVA treatment may protect against PDR by regulating HBB, HPX, VEGFA, and CA1 expression.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.

[Effects of rapid drug sensitivity testing for multidrug-resistant bacteria on the prognosis of patients with severe intra-abdominal infection].

Objective: To examine the clinical value of rapid detection of drug-resistant bacteria by immunochromatography and the effects of rapid detection on the prognosis of patients with severe intra-abdominal infection complicated by carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection. Methods: This was a retrospective cohort study. We analyzed clinical data of 73 patients with severe abdominal infections with sepsis or septic shock complicated by CRE bloodstream infection admitted to the general surgery department of Jinling Hospital between February 2022 and February 2023. Patients were divided into a colloidal gold immunochromatographic assay (GICA) group (17 patients) and conventional testing group (56 patients) based on whether a GICA for CRE had been performed on the patients' first blood culture sample during the diagnosis and treatment process. There were no statistically significant differences between the GICA and conventional testing groups in age ([55.9±17.3] vs. [47.6±16.4] years), sex ([16 men vs. one woman ] vs. [41 men vs. 15 women]), median Charlson comorbidity index (3.0[2.0,4.0] vs. 3.0[2.0, 4.8]), septic shock (10 vs. 39), or acute kidney injury (8 vs. 40) (all P>0.05). Both groups routinely underwent traditional bacterial identification and drug susceptibility testing. Additionally, patients in the GICA group were tested directly for positive blood cultures using a GICA carbapenemase test kit. The main outcomes were mortality rates on Days 28 and 90 after the first identification of CRE bloodstream infection in both groups. We also compared the microbial clearance rate, duration of hospitalization and intensive care unit stay, and time from onset of CRE bloodstream infection to initiation of targeted and appropriate antibiotics between the two groups. Results: The rate of microbial clearance of bloodstream infection was significantly greater in the GICA group than in the conventional testing group (15/17 vs. 34/56 [60.7%], χ2=4.476, P=0.034), whereas the 28-day mortality tended to be lower in the GICA than conventional testing group [5/17 vs. 44.6% [25/56], χ2=1.250, P=0.264). The 90-day mortality (8/17 vs. 53.6% [30/56], χ2=0.222, P=0.638), median duration of hospitalization (37.0 [18.0, 46.5] days vs. 45.5 [32.2, 64.8] days, Z=-1.867, P=0.062), and median duration of intensive care unit stay (18.0 [6.5, 35.0] days vs. 32.0 [5.0, 51.8] days, Z=-1.251, P=0.209). The median time between the onset of bloodstream infection and administration of antibiotics was 49.0 (38.0, 69.0) hours in the GICA group, which is significantly shorter than the 163.0 (111.8, 190.0) hours in the conventional testing group (Z=-5.731, P<0.001). The median time between the onset of bloodstream infection and administration of appropriate antibiotics was 40.0 (34.0, 80.0) hours in the GICA group, which is shorter than in the conventional testing group (68.0 [38.2, 118.8]) hours; however, this difference is not statistically significant (Z=-1.686, P=0.093). Conclusions: GICA can provide information on carbapenemase- producing pathogens faster than traditional drug sensitivity testing, enabling early administration of the optimal antibiotics. The strategy of 'carbapenemase detection first' for managing bacterial infection has the potential to improve prognosis of patients and reduce mortality rate.

[Efficacy and safety of extracorporeal membrane oxygenation-supported percutaneous coronary intervention in chronic coronary total occlusion patients with reduced left ventricular ejection fraction].

Objective: To investigate the feasibility and safety of extracorporeal membrane oxygenation (ECMO)-supported percutaneous coronary intervention (PCI) in chronic coronary total occlusion (CTO) patients with reduced left ventricular ejection fraction (LVEF). Methods: The CTO patients with LVEF≤35% and undergoing CTO-PCI assisted by ECMO in the General Hospital of Northern Theater Command from December 2018 to March 2022 were enrolled in this study. The post-procedure complications, changes of LVEF from pre-procedure to post-procedure during hospitalization, and the incidence of all-cause mortality and changes of LVEF after discharge were assessed. Results: A total of 17 patients aged (59.4±11.8) years were included. There were 14 males. The pre-procedure LVEF of these patients were (29.00±4.08)%. Coronary angiography results showed that there were 29 CTO lesions in these 17 patients. There was 1 in left main coronary artery, 7 in left anterior descending artery, 11 in left circumflex artery, and 10 in right coronary artery. ECMO was implanted in all patients before procedure. Among 25 CTO lesions attempted to cross, 24 CTO were successfully implanted with stents. All patients underwent successful PCI for at least one CTO lesion. The number of drug-eluting stents implantation per patient were 4.6±1.3. After procedure, there were 8 patients with hemoglobin decreased>20 g/L, and 1 patient with ECMO-access-site related bleeding. The LVEF value at a median duration of 2.5 (2.0-5.5) days after procedure significantly increased to (38.73±7.01)% (P<0.001 vs. baseline). There were no in-hospital deaths. Patients were followed up for 360 (120, 394) days after discharge, 3 patients died (3/17). The LVEF value was (41.80±7.32)% at 155 (100, 308) days after discharge, which was significantly higher than the baseline value (P<0.001). Conclusion: The results of present study demonstrate that it is feasible, efficient and safe to perform ECMO)-supported CTO-PCI in CTO patients with reduced LVEF.

Expanded quantum vortex liquid regimes in the electron nematic superconductors FeSe1-xSx and FeSe1-xTex.

The quantum vortex liquid (QVL) is an intriguing state of type-II superconductors in which intense quantum fluctuations of the superconducting (SC) order parameter destroy the Abrikosov lattice even at very low temperatures. Such a state has only rarely been observed, however, and remains poorly understood. One of the key questions is the precise origin of such intense quantum fluctuations and the role of nearby non-SC phases or quantum critical points in amplifying these effects. Here we report a high-field magnetotransport study of FeSe1-xSx and FeSe1-xTex which show a broad QVL regime both within and beyond their respective electron nematic phases. A clear correlation is found between the extent of the QVL and the strength of the superconductivity. This comparative study enables us to identify the essential elements that promote the QVL regime in unconventional superconductors and to demonstrate that the QVL regime itself is most extended wherever superconductivity is weakest.

[The efficacy and safety analysis of cervical and abdominal double single-port minimally invasive esophagectomy].

Objective: To summarize the efficacy and safety of minimally invasive esophagectomy through cervical and abdominal double single-port. Methods: A total of 28 patients who underwent cervical and abdominal double single-port minimally invasive radical resection of esophageal cancer from January 2021 to October 2022 in the First Affiliated Hospital of Fujian Medical University were retrospectively collected, including 18 males and 10 females, aged 58-80 (72±4) years. All patients were placed in the supine position, the single port was operated through the cervical mediastinum first, then the single port was operated through the abdominal cavity, and finally the neck was anastomosed. The operative time, intraoperative blood loss, postoperative ambulation time, postoperative drainage tube removal time, postoperative complications, postoperative pathological examination results, postoperative discharge time of patients were recorded and followed. Results: In the included 28 patients, there were twenty-six patients successfully completed the cervical and abdominal double single-port minimally invasive radical resection of esophageal cancer, and two patients were transferred to the right thoracoscopic surgery due to oozing of blood and unclear visual field, without conversion to laparotomy or enlargement of the incision occurred. The operation time was 125 to 215 (152±32) minutes, including 43 to 100 (56±15) minutes in the mediastinum and 35 to 63 (40±5) minutes in the abdominal cavity. Intra-operative blood loss was 55-100 (45±20) ml. There were 8 to 14 (11±3) lymph nodes dissected in the mediastinum and 7 to 15 (9±3) lymph nodes dissected in the abdominal cavity. Twenty-eight patients were active in bed 1 to 2 days after surgery. The left cervical drainage tube was removed 2 days after surgery. There was no anastomotic fistula, anastomotic stenosis, pulmonary infection, chylothorax and stomach emptying disorder in the whole group. Pleural effusion occurred in 4 cases, all of them had pleural damage during the operation, and were cured after postoperative puncture and drainage; two cases had hoarseness and one case had cough after eating, all patients were discharged from hospital after eating liquid. Postoperative hospital median stay was [ M(Q1, Q3)] 7(6, 9) d. The postoperative pathological examination results of all patients were squamous cell carcinoma, and the postoperative pathological stage was pT1-3N0-1M0. The median postoperative follow-up was 25 (5, 35) months, and no patients had complications, recurrence, metastasis or death during the follow-up period. Conclusion: The cervical and abdominal double single-hole minimally invasive radical resection of esophageal cancer is safe and feasible, with good short-term efficacy, which provide an opportunity for radical surgery for patients with advanced age, poor cardiopulmonary function or insufficient thoracic conditions.

Succession of the microbial communities and metabolic functions in composting or deep burial processing of dead chickens.

1. This study examined the effects of composting and deep burial techniques on degradation efficiency of dead chickens. Different raw materials (crushed branches or rape straws) and disinfectants (quicklime or bleaching powder) were applied in composting and deep burial process, respectively. The whole process lasted for 90 d in both summer and winter.2. High throughput sequencing displayed that Firmicutes, Proteobacteria, Bacteroidetes, Actinobacteria and Deinococcus-Thermus were the most dominant bacterial phyla during the experiment. The relative abundance of Firmicutes dwindled gradually with prolonged composting duration, while Proteobacteria, Bacteroidetes and Deinococcus-Thermous increased gradually over time.3. The bacterial functions identified from the KEGG pathway showed that amino acid and carbohydrate metabolism were the major microbial metabolic pathways that determined final degradation efficiency. At the end of the trial, the decomposition status of chicken carcases and faecal coliforms were measured.4. The results demonstrated that the optimum decomposition effect was obtained in composting compared with other treatment groups. Low ambient temperature reduced degradation efficiency, due to restricted microbial activity. In addition, faecal coliforms were not completely removed by the deep burial process of dead chickens in winter.5. These findings provide a theoretical basis for the feasibility of composting chicken carcases instead of deep burial.

Air quality improvement assessment and exposure risk of Shandong Province in China during 2014 to 2020.

As one of the most polluted provinces in China, air pollution events occur frequently in Shandong. Based on the hourly (or daily) concentrations of six air pollutants (PM2.5, PM10, O3, NO2, SO2 and CO), the situations of air quality improvement in three kinds of cities (key cities, coastal cities and general cities) are assessed comprehensively during 2014-2020. Contrary to the daily maximum 8-h average ozone (MDA8 O3), the annual average concentrations of other pollutants show the downward trends during 2014-2020. Therein, the improvement rates of annual average concentrations of air pollutants in key cities are highest. By 2020, the day proportions of O3 as the primary pollutant are up to 38% in three kinds of cities. Besides, due to the impact of COVID-19, the monthly average concentrations of PM2.5, PM10, NO2, SO2 and CO in February 2020 decrease by 32.1-49.5% year-on-year. There are still about 50% of population exposed to high-risk regions (R i > 2), which are mainly concentrated in main urban areas and industrial areas. Thus, the adjustment of industrial structure and energy composition in the context of carbon peak and carbon neutrality should be implemented in the future. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04651-5.

[Clinical outcomes of transoral endoscopic thyroidectomy vestibular approach assisted with submental mini-incision for early thyroid papillary carcinoma].

Objective: To investigate the efficacy of transoral endoscopic thyroidectomy vestibular approach (TOETVA) assisted with submental mini-incision in early thyroid papillary carcinoma. Methods: A total of 63 patients with early papillary thyroid carcinoma (cT1N0M0) were included who underwent TOETVA from December 2019 to May 2021 in Department of Thyroid Surgery of the Affiliated Hospital of Jining Medical University. There were 4 males and 59 females, aged from 17 to 46 years old. Of those 36 patients received traditional TOETVA as control and 27 patients accepted modified TOETVA assisted with submental mini-incision. The clinical outcomes of patients in two groups were compared. Chi-square test and t test were used in statistical analyses. Results: Compared to control group, modified TOETVA group had the less mean operation time [(146.63±38.62) minutes vs. (167.78±36.71) minutes, t=-2.21, P=0.031], the shorter time required for returning to normal diet after operation [(2.11±0.89) days vs. (2.72±1.16) days, t=-2.28, P=0.026], and the lower probability of mandibular numbness (0 vs. 16.67%, χ2=4.97, P=0.026). There was no significant difference between two groups in intraoperative blood loss, postoperative drainage volume, number of central lymph nodes dissection, and postoperative complications such as gas embolism, postoperative bleeding, postoperative infection, skin burns, subcutaneous effusion and so on(all P>0.05). After 6 months of operation, the thyroid ultrasound of the patients in two groups showed no recurrence, and the patients were satisfied with their surgical incision appearances. Conclusion: Both the modified and traditional TOETVA show similar efficacies for treatments of early thyroid papillary carcinoma, but the modified TOETVA can reduce the operation time and improve the quality of life.

[Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma].

OBJECTIVE: To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification. METHODS: A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk. RESULTS: Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis. CONCLUSION: MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

[Hyper-IgE syndrome in adults characterized by disseminated mixed infection: a case report and literature review].

Objective: To improve the awareness of hyper-IgE syndrome (HIES) characterized by disseminated infection. Methods: We retrospectively analyzed a patient with HIES characterized by Talaromyces marneffei and Staphylococcus aureus mixed disseminated infection in Shenzhen People's Hospital. The clinical manifestations, results of laboratory tests/genetic examinations, therapeutic strategies and prognosis were summarized. The keywords "hyper-lgE syndrome" were used to search and review the literature in Wanfang databases and Pubmed database. Results: In February 2021, an 18-year-old male patient was admitted to our hospital with backache for over 3 weeks and fever for 4 days. Physical examination revealed deciduous teeth in the oral cavity, bilateral renal pain on percussion, and interphalangeal joint hyperextension. Laboratory studies demonstrated increased blood eosinophils and serum level of total IgE. Bacterial culture from bronchoscopic secretions, bronchial mucosa, and necrotic tissue from the left upper arm showed Talaromyces marneffei. Bacterial culture from alveolar lavage fluid, left upper arm necrotic tissue, puncture fluid of right retroauricular abscess and renal drainage fluid suggested methicillin-sensitive Staphylococcus aureus. The chest and abdominal CT revealed diffuse patchy and nodular lesions in bilateral lungs, cavitary lesions in the upper lobe of the left lung, multiple enlarged lymph nodes in the mediastinum, and infectious lesions within both kidneys and perirenal space. Furthermore, the patients was identified with STAT3 mutations by whole exome sequencing, which confirmed the diagnosis of HIES. Nineteen literature articles were retrieved, involving 27 adult patients with a median age of diagnosis of 23 years. The most common manifestations included: skin infection (16/27), eczema (15/27), elevated IgE (26/27) and eosinophils (17/27), as well as positive STAT3 mutation (11/27). Conclusion: Clinicians should be alert to the possibility of hyper-IgE syndrome in patients with severe or disseminated intracellular bacterial infections.

Changes of blood flow in macular zone of patients with diabetic retinopathy at different stages evaluated by optical coherence tomography angiography.

PURPOSE: To evaluate changes in macular blood flow in patients with various stages of diabetic retinopathy (DR) by optical coherence tomography angiography (OCTA). MATERIALS AND METHODS: The data of 94 patients (122 eyes) with type 2 diabetes mellitus admitted from January 2018 to May 2021 were recorded, including 31 patients (42 eyes) with no DR (NDR group), 33 patients (40 eyes) with mild non-proliferative DR (mild NPDR group) and 30 patients (40 eyes) with moderate NPDR (moderate NPDR group). Forty healthy patients (40 eyes) who were examined during the same period were selected as control group. The blood flow densities at the superficial capillary plexus (SCP), deep capillary plexus (DCP) and 300µm-wide region near the foveal avascular zone (FAZ) (FD300), FAZ area, FAZ perimeter and acircularity index (AI) were compared. Correlations of blood flow densities at the SCP, DCP and FD300, FAZ area, FAZ perimeter and AI with the severity of DR were investigated by multivariate regression analysis. A receiver operating characteristic (ROC) curve was plotted to analyze the predictive efficacy of the OCTA indices for early DR. RESULTS: Blood flow densities at the SCP, DCP and FD300 significantly decreased, while FAZ perimeter and AI increased in the NDR and DR groups compared with those of the control group (P<0.05). Blood flow densities at the SCP, DCP and FD300 of the DR group were lower than those of the NDR group, but the FAZ perimeter and AI of the former were larger (P<0.05). Blood flow densities at the SCP, DCP and FD300 in the macular zone of DR patients declined with increasing DR stage, while FAZ perimeter and AI increased (P<0.05), without collinearity among the variables. The area under the curve of FD300 for predicting early DR was highest (0.804), with a sensitivity and specificity of 84.13% and 67.19%, respectively. AI with a cut-off value of 1.05 showed the optimal specificity (87.84%) and sensitivity (73.62%) for predicting early DR. CONCLUSIONS: The flow density at FD300 declines, while FAZ perimeter and AI increase in the macular zone of patients with early DR. These three OCTA indicators show close associations with DR stage, and can function as predictors of early DR.

Particle trapped at the isotropic-nematic liquid crystal interface: Elastocapillary phenomena and drag forces.

We present numerical simulations of a particle trapped at the isotropic-nematic liquid crystal (Iso-N) interface. We use our recent model, based on a phase-field approach [see Qiu et al., Phys. Rev. E 103, 022706 (2021)10.1103/PhysRevE.103.022706], to couple the capillary forces acting on the interface with the elastic stresses in the nematic phase along with topological defects. A range of floating configurations are first investigated as a function of the contact angle and various anchoring conditions at the fluid interface. The results show that the response of the system is driven by the existence of an anchoring conflict at the contact line. Substantial particle displacements and/or interfacial deformations may occur in this case even for moderate anchoring strengths. These findings highlight the coupling between elastic and capillary forces. In a second part, we compute drag forces exerted on a particle that moves along the Iso-N interface for several contact angles and a moderate Ericksen number. Because of the coupling between the velocity and order parameter fields, topological defects are swept downstream of the particle by the flow and sometimes escape from the particle or merge with the interface. We also find linear force-velocity laws, with drag forces at the Iso-N interface being slightly greater than their isotropic counterparts due to director distortions. We discuss these results in light of past studies on the behavior of particles being dragged in the bulk of a liquid crystal matrix.

[Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China].

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.

[Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men].

Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.

Clinical progress and advanced research of red blood cells based drug delivery system.

Red blood cells (RBCs) are biocompatible carriers that can be employed to deliver different bioactive substances. In the past few decades, many strategies have been developed to encapsulate or attach drugs to RBCs. Osmotic-based encapsulation methods have been industrialized recently, and some encapsulated RBC formulations have reached the clinical stage for treating tumors and neurological diseases. Inspired by the intrinsic properties of intact RBCs, some advanced delivery strategies have also been proposed. These delivery systems combine RBCs with other novel systems to further exploit and expand the application of RBCs. This review summarizes the clinical progress of drugs encapsulated into intact RBCs, focusing on the loading and clinical trials. It also introduces the latest advanced research based on developing prospects and limitations of intact RBCs drug delivery system (DDS), hoping to provide a reference for related research fields and further application potential of intact RBCs based drug delivery system.