Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Objective:To investigate the epidemiological and clinical characteristics of human parainfluenza viruses (HPIVs) infection among hospitalized children with community-acquired pneumonia (CAP) in China, and provide basic data for diagnosis, treatment and prevention of HPIVs infection.Methods:From November 2014 to February 2020, 5 448 hospitalized children with CAP were enrolled in 14 hospitals in 11 provinces and municipalities directly under the Central Government in southern China and northern China. Nasopharyngeal aspirates or throat swabs were collected, and the nucleic acids of 18 types respiratory viruses including HPIV1-4 were screened by suspension array technology. Demographic data and clinical information were collected for statistical analysis.Results:The total detection rate of HPIVs in 5 448 children with CAP was 8.83% (481/5 448), and the detection rate in males was higher than that in females (62.79% vs. 37.21%; χ2=0.000, P=0.992). The detection rate of HPIVs in 1~< 3 years age group was higher than that in other age groups, and the difference was statistically significant ( χ2=61.893, P<0.001). The detection rate of HPIVs in the northern region was higher than that in the southern region (9.02% vs 8.65%), but the difference was not statistically significant ( χ2=0.239, P=0.625). The prevalence of HPIV1-4 in northern and southern China was not completely same. HPIV1 was mainly prevalent in autumn in both northern and southern regions. HPIV2 was prevalent in summer in northern China, and the detection rate was low in southern China. HPIV3 reached its peak in both spring and summer in both northern and southern China, but its duration was longer in southern China than in northern China. HPIV4 is mainly popular in autumn in both southern China and northern China. Among 481 children infected with HPIVs, 58.42% (281/481) were infected with HPIV alone, and the main clinical manifestations were cough (90.75%) and fever (68.68%). Out of the HPIV-positive cases, 42.62% (205/481) were co-infected with another type of HPIV or a different virus, while 11.43% (55/481) had co-infections with two or more different viruses. HPIV3 was the most common type of co-infection with other viruses. HPIV3 infection accounted for the largest proportion (76.80%) in 47 HPIVs-positive children with severe pneumonia. Conclusions:HPIVs is one of the most important pathogens causing CAP in children in China, and children under 3 years of age are the main populations of HPIVs infection. The prevalence characteristics of all types of HPIVs in children in the north and south are not completely same. HPIV3 is the dominant type of HPIV infections and causes more severe diseases.

Objective To investigate the effect of long non-coding RNA (IncRNA) nuclear-enriched abundant transcript 1 (NEATl) on hypoxia-reoxygenation (H/R) glial astrocyte injury, and to explore whether the mechanism was related to the regulation of micro RNA (miR)-761. Methods Rat cortical astrocytes were cultured to construct a H/R injury model. Astrocytes were divided into control group, model group, model+ small interfering RNA negative control (si-NC) group, model+ si-NEATl group, model+ miR-NC group, model + miR-761 group, model + si-NEATl + anti-miR-NC group, model+si-NEATl+anti-miR-761 group. Expression of NEATl and miR-761 were detected by Real-time PCR. The experiment was repeated 3 times. The content of malonaldefryde (MDA), and the activity of superoxide dismutase (SOD) and catalase (CAT) were detected by kits. Dual luciferase reporter experiment and Real-time PCR were used to analyze the targeting relationship between NEATl and miR-761. The experiment was repeated 3 times. Results Compared with the control group, the cell apoptosis rate and MDA content of the model group increased significantly, SOD and CAT activities decreased significantly, NEATl expression increased significantly, and miR-761 expression decreased significantly (P< 0. 05). Compared with the model+si-NC group, the apoptosis rate and MDA content of the model+si-NEATl group reduced significantly, and SOD and CAT activities increased significantly (P < 0 . 0 5) . Compared with the model + miR-NC group, the apoptosis rate and MDA content of the model + miR-761 group reduced significantly, and SOD and CAT activities increased significantly (P < 0 . 0 5) . MiR-761 was the target gene of N E A T l, and NEATl negatively regulated miR-761 expression. Compared with the model+si-NEATl+anti-miR-NC group, the apoptosis rate and MDA content of the model+siNEAT1+anti-miR-761 group increased significantly, and SOD and CAT activities decreased significantly (P < 0 . 0 5) . Conclusion Interference with NEATl expression can protect astrocytes from H / R injury by up-regulating miR-761.

Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. Nuclear factor erythroid 2-related factor 2 (NRF2) activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

Prostate cancer (PCa) is the second-most common cancer among men. Both active surveillance or watchful waiting (AS/WW) and focal laser ablation (FLA) can avoid the complications caused by radical treatment. How to make the choice between these options in clinical practice needs further study. Therefore, this study aims to compare and analyze their effects based on overall survival (OS) and cancer-specific survival (CSS) to obtain better long-term benefits. We included patients with low-risk PCa from the Surveillance Epidemiology and End Results database of 2010-2016. Multivariate Cox proportional hazard analyses were conducted for OS and CSS in the two groups. To eliminate bias, this study applied a series of sensitivity analyses. Moreover, Kaplan-Meier curves were plotted to obtain survival status. A total of 18 841 patients with low-risk PCa were included, with a median of 36-month follow-up. According to the multivariate Cox proportional hazard regression, the FLA group presented inferior survival benefits in OS than the AS/WW group (hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.37-3.33, P < 0.05). After adjusting for confounders, the result persisted (HR: 1.69, 95% CI: 1.02-2.81, P < 0.05). According to the results of the sensitivity analysis, the inverse probability of the treatment weighing model indicated the same result in OS. In conclusion, AS/WW and FLA have the advantage of fewer side effects and the benefit of avoiding overtreatment compared with standard treatment. Our study suggested that AS/WW provides more survival benefits for patients with low-risk PCa. More relevant researches and data will be needed for further clarity.
Humans ; Laser Therapy ; Male ; Proportional Hazards Models ; Prostatectomy ; Prostatic Neoplasms ; Risk ; Watchful Waiting

Objective: To compare the outcomes of modified Appleby procedure and sub-adventitial divestment technique for locally advanced or borderline resectable pancreatic body cancer. Methods: A total of consecutive 58 patients(33 males and 25 females) who were diagnosed as locally advanced or borderline resectable pancreatic body cancer and underwent distal pancreatectomy at Pancreas Center, First Affiliated Hospital of Nanjing Medical University between September 2013 and May 2019 were retrospectively reviewed. The age(M(IQR)) was 62(9)years(range: 43 to 79 years). Thirty-one patients underwent distal pancreatectomy with celiac axis resection (DP-CAR) and 27 patients underwent distal pancreatectomy with sub-adventitial divestment technique(SDT). Perioperative parameters and follow-up data of these patients were analyzed. Quantitative data were compared with Wilcoxon test while categorical variables were compared with χ² test or Fisher's exact test. Survival results were estimated by the Kaplan-Meier survival method with a Log-rank test. Results: There were no differences in age,gender,body mass index,abdominal symptoms,comorbidity or preoperative serum CA19-9 between two groups(all P>0.05). Obvious preoperative weight loss was more common in the group of SDT(48.1%(13/27) vs. 19.4%(6/31),χ²=5.431,P=0.020). Longer operative time(310(123) minutes vs. 254(137)minutes, Z=2.277,P=0.023),higher rate of combined organ resection(41.9%(13/31) vs. 14.8%(4/27),χ²=5.123,P=0.041) and longer postoperative hospital stay(15(10) days vs. 11(5)days,Z=2.292,P=0.022) were observed in the group of DP-CAR. Moreover,rate of overall morbidities was also higher (71.0%(22/31) vs. 29.6%(8/27),χ²=9.876,P=0.003),implicated by clinically relevant postoperative pancreatic fistula(61.3%(19/31) vs. 29.6%(8/27),χ²=5.814,P=0.020) in the DP-CAR group. Tumor size of the DP-CAR group was bigger(4.9(1.5)cm vs. 4.0(1.2)cm,Z=2.343,P=0.019) but no difference was seen between the DP-CAR group and SDT group in R0+R1(<1 mm) resection rate (84.0%(21/25) vs. 90.0%(18/20),P=0.678) and LNR(12.0(23.0)% vs. 9.0(18.0)%,Z=1.238,P=0.216),as well as median disease free survival(11.7 months vs. 11.4 months,Z=0.019,P=0.892) and median overall survival(16.3 months vs. 13.7 months,Z=0.172,P=0.679). Conclusions: Both DP-CAR and distal pancreatectomy with SDT are relatively safe and feasible for locally advanced or borderline resectable pancreatic body cancer. Compared with arterial resection,SDT may contribute to lower rates of postoperative complications and shorter duration of hospitalization,but no significant benefit is seen in long-term survival.
Celiac Artery/surgery* ; Female ; Humans ; Male ; Pancreatectomy/methods* ; Pancreatic Neoplasms/pathology* ; Postoperative Complications ; Retrospective Studies