[Investigation of the immune profile of multiple myeloma patients achieving long-term survival after autologous stem cell transplantation].

Objective: To identify the characteristics of the bone marrow immune microenvironment associated with long-term survival in multiple myeloma (MM) patients. Methods: In the follow-up cohort of patients with newly diagnosed MM and who received "novel agent induction therapy and subsequent autologous stem cell transplantation and immunomodulator maintenance therapy" in the First Affiliated Hospital of Sun Yat-sen University, a cross-sectional study was carried out between August 2019 and May 2020. Using NanoString technology, the RNA expression of 770 bone marrow immune-related markers was compared between 16 patients who had progression-free survival ≥5 years and 5 patients with progressive disease. Among the 16 patients who achieved long-term survival, 9 achieved persistent minimal residual disease (MRD) negative while the other 7 had persistent positive MRD. The functional scores of each kind of immune cells were calculated based on the expression level of characteristic genes, so as to indirectly obtained the proportion of each immune cell subset. The Mann-Whitney U test and the Kruskal Wallis test were used for statistical analysis. Results: The proportion of neutrophils was significantly higher in long-surviving MM patients than in patients with progressive disease [functional scores, 13.61 (13.33, 14.25) vs. 12.93 (12.58, 13.38); Z=2.31, P=0.021]. Among long-surviving patients, those who were MRD-positive had a significantly greater number of mast cells compared with those who were MRD-negative [functional scores, 7.09 (6.49, 8.57) vs. 6.03 (5.18, 6.69); H=2.18, P=0.029]. Compared with patients with progressive disease, four genes (CTSG, IFIT2, S100B, and CHIT1) were significantly downregulated and six (C4B, TNFRSF17, CD70, IRF4, C2, and GAGE1) were upregulated in long-surviving patients. Among long-surviving patients, only gene CMA1 was significantly upgraded, 10 genes (ISG15, OAS3, MX1, IFIT2, DDX58, SIGLEC1, CXCL10, IL1RN, SERPING and TNFSF10) were significantly downregulated in the MRD-positive group compared with that in the MRD-negative group, the first 5 of which are related to the interferon response pathway. Conclusions: The increased neutrophil and mast cell numbers may be related to long-term survival in MM. Interferon signaling activation may be a key bone marrow immune profiling feature for MRD-negative, long-surviving patients with MM.

Improving chilling tolerance of peanut seedlings by enhancing antioxidant-modulated ROS scavenging ability, alleviating photosynthetic inhibition, and mobilizing nutrient absorption.

Peanut production is threatened by climate change. Damage to seedlings from low temperatures in early spring can limit yield. Plant adaptations to chilling stress remain unclear in peanut seedlings. It is essential to understand how peanut acquires chilling tolerance. We evaluated effects of chilling stress on growth and recovery of peanut seedlings. We compared and analysed biological characteristics, antioxidants, photosynthesis, biochemical and physiological responses, and nutrient absorption at varying levels of chilling. Compared with chilling-sensitive FH18, the reduced impact of chilling stress on chilling-tolerant NH5 was associated with reduced ROS accumulation, higher ascorbate peroxidase activity and soluble sugar content, lower soluble protein content, and smaller reductions in nutrient content during stress. After removal of chilling stress, FH18 had significant accumulation of O2 •- and H2O2, which decreased photosynthesis, nutrient absorption, and transport. ROS-scavenging reduced damage from chilling stress, allowed remobilization of nutrients, improved chilling tolerance, and restored plant functioning after chilling stress removal. These findings provide a reference for targeted research on peanut seedling tolerance to chilling and lay the foundation for bioinformatics-based research on peanut chilling tolerance mechanisms.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Analysis of etiology and complications in children with stage 5 chronic kidney disease].

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.

[Spatial distribution of Oncomelania hupensis spread in Hubei Province from 2020 to 2022].

OBJECTIVE: To identify the spatial distribution pattern of Oncomelania hupensis spread in Hubei Province, so as to provide insights into precision O. hupensis snail control in the province. METHODS: Data pertaining to emerging and reemerging snails were collected from Hubei Province from 2020 to 2022 to build a spatial database of O. hupensis snail spread. The spatial clustering of O. hupensis snail spread was identified using global and local spatial autocorrelation analyses, and the hot spots of snail spread were identified using kernel density estimation. In addition, the correlation between environments with snail spread and the distance from the Yangtze River was evaluated using nearest-neighbor analysis and Spearman correlation analysis. RESULTS: O. hupensis snail spread mainly occurred along the Yangtze River and Jianghan Plain in Hubei Province from 2020 to 2022, with a total spread area of 4 320.63 hm2, including 1 230.77 hm2 emerging snail habitats and 3 089.87 hm2 reemerging snail habitats. Global spatial autocorrelation analysis showed spatial autocorrelation in the O. hupensis snail spread in Hubei Province in 2020 and 2021, appearing a spatial clustering pattern (Moran's I = 0.003 593 and 0.060 973, both P values < 0.05), and the mean density of spread snails showed spatial aggregation in Hubei Province in 2020 (Moran's I = 0.512 856, P < 0.05). Local spatial autocorrelation analysis showed that the high-high clustering areas of spread snails were mainly distributed in 50 settings of 10 counties (districts) in Hubei Province from 2020 to 2022, and the high-high clustering areas of the mean density of spread snails were predominantly found in 219 snail habitats in four counties of Jiangling, Honghu, Yangxin and Gong'an. Kernel density estimation showed that there were high-, secondary high- and medium-density hot spots in snail spread areas in Hubei Province from 2020 to 2022, which were distributed in Jingzhou District, Wuxue District, Honghu County and Huangzhou District, respectively. There were high- and medium-density hot spots in the mean density of spread snails, which were located in Jiangling County, Honghu County and Yangxin County, respectively. In addition, the snail spread areas negatively correlated with the distance from the Yangtze River (r = -0.108 9, P < 0.05). CONCLUSIONS: There was spatial clustering of O. hupensis snail spread in Hubei Province from 2020 to 2022. The monitoring and control of O. hupensis snails require to be reinforced in the clustering areas, notably in inner embankments to prevent reemerging schistosomiasis.

Unveiling new quantum phases in the Shastry-Sutherland compound SrCu2(BO3)2 up to the saturation magnetic field.

Under magnetic fields, quantum magnets often undergo exotic phase transitions with various kinds of order. The discovery of a sequence of fractional magnetization plateaus in the Shastry-Sutherland compound SrCu2(BO3)2 has played a central role in the high-field research on quantum materials, but so far this system could only be probed up to half the saturation value of the magnetization. Here, we report the first experimental and theoretical investigation of this compound up to the saturation magnetic field of 140 T and beyond. Using ultrasound and magnetostriction techniques combined with extensive tensor-network calculations (iPEPS), several spin-supersolid phases are revealed between the 1/2 plateau and saturation (1/1 plateau). Quite remarkably, the sound velocity of the 1/2 plateau exhibits a drastic decrease of -50%, related to the tetragonal-to-orthorhombic instability of the checkerboard-type magnon crystal. The unveiled nature of this paradigmatic quantum system is a new milestone for exploring exotic quantum states of matter emerging in extreme conditions.

[Clinical application of flexible bronchoscopy in the treatment of airway foreign body].

Airway foreign body is the unintentional entry of objects into the larynx, trachea, or bronchi, causing airway obstruction, severe coughing, wheezing, breathing difficulties, or even asphyxiation. It is a common emergency condition in respiratory, critical care, emergency, otolaryngology, and pediatric departments, etc. With the popularization of flexible bronchoscopic techniques, endoscopic foreign body removal has been widely used in adults and children. The combined application of various instruments, such as alligator forceps, mesh baskets, balloons, and cryoprobes could safely and effectively remove foreign body. This article briefly described the treatment modalities for airway foreign body and summarized effective approaches using flexible bronchoscopy in its treatment.

[Clinical application and progress of airway stent in subglottic stenosis].

Laryngotracheal stenosis is caused by various reasons of laryngotracheal cartilage stent malformation, collapse or defect, laryngotracheal mucosa scar formation or submucosal tissue hyperplasia, eventually resulting in dyspnea. Subglottic stenosis refers to the airway stenosis from subglottic to the lower margin of the cricoid cartilage, which is a special type of laryngotracheal stenosis. The most common cause is iatrogenic injury, such as prolonged tracheal intubation and tracheotomy. Currently, the main treatments include surgical treatment, tracheostomy, endoscope-guided stent implantation and drug therapy. As for the patients who have dyspnea not suitable for surgery or in urgent need of preoperative transitional treatment, stent implantation guided by respiratory endoscopy has become an important treatment. In this paper, we reviewed 51 literatures on stent implantation of subglottic stenosis since 1994 retrieved from PubMed, CBM, CNIT, Wan-fang and VIP databases, focusing on the comparison of the efficacy, complications and prognosis of metal stent, hourglass-shaped DUMON stent, straight-type DUMON stent and Montgomery T tube and investigated the clinical application of endoscope-guided stent implantation in subglottic airway stenosis. Literature studies have shown that compared with DUMON silicone stents and metal stents, T tube has more significant advantages, higher treatment success rate and lower complication rate. Therefore, Montgomery T tube is more suitable for long-term treatment of patients with subglottic stenosis. With the improvement and update of new technology and materials, the vigorous development of new airway stents also provides a new stent treatment mode with better histocompatibility, fewer complications and customized options for the patients with subglottic stenosis.

[Independent and joint effect of chronotype and sleep duration on self-rated health in medical students].

Objective: To investigate the independent and joint effects of chronotype and sleep duration on self-rated health in medical students. Methods: A cross-sectional study was conducted in 1 526 medical students selected through proportional stratified cluster random sampling from a medical university in Zhejiang province. A questionnaire survey was conducted to collect the information about their basic demographic characteristics, chronotype, sleep duration, and other lifestyle factors such as midnight snack, sedentary behavior, physical activity, meal time, and self-rated health. The independent and joint effects of chronotype and sleep duration on self-rated health were assessed by logistic regression model after controlling for confounding variables. Results: The numbers of the students with evening chronotype, neutral chronotype, and morning chronotype were 664 (43.5%), 442 (29.0%), and 420 (27.5%), respectively. Among the medical students, 42.8% (653) had poor self-rated health. Compared with those with the morning chronotype, the adjusted ORs for those with neutral chronotype and evening chronotype were 1.69 (95%CI: 1.23-2.31) and 2.43 (95%CI: 1.81-3.26), respectively, trend test P<0.001. Compared with those with sleep duration of 8 h or above per night, the adjusted ORs for those with sleep duration of 7 and ≤6 h per night were 1.40 (95%CI: 1.07-1.84) and 2.38 (95%CI: 1.69-3.37), respectively, trend test P<0.001. In the joint effect, compared with those with the morning chronotype and sleep duration of 8 h or above per night, the adjusted OR for those with evening chronotype and sleep duration of ≤6 h per night was 6.53 (95%CI: 3.53-12.09). Conclusions: Both evening chronotype and insufficient sleep were associated with increased odds of poor self-rated health in medical students, and they had joint effects. Therefore, it is necessary to promote early to bed, early to rise and adequate sleep in medical student to maintain their health.

Magnetically Hidden State on the Ground Floor of the Magnetic Devil's Staircase.

We investigated the low-temperature and high-field thermodynamic and ultrasonic properties of SrCu_{2}(BO_{3})_{2}, which exhibits various plateaux in its magnetization curve above 27 T, called a magnetic Devil's staircase. The results of the present study confirm that magnetic crystallization, the first step of the staircase, occurs above 27 T as a first-order transition accompanied by a sharp singularity in heat capacity C_{p} and a kink in the elastic constant. In addition, we observe a thermodynamic anomaly at lower fields around 26 T, which has not been previously detected by any magnetic probes. At low temperatures, this magnetically hidden state has a large entropy and does not exhibit Schottky-type gapped behavior, which suggests the existence of low-energy collective excitations. Based on our observations and theoretical predictions, we propose that magnetic quadrupoles form a spin-nematic state around 26 T as a hidden state on the ground floor of the magnetic Devil's staircase.

[Epidemiological trends for human schistosomiasis prevalence in Hubei Province from 2004 to 2018 based on Joinpoint regression analysis].

OBJECTIVE: To analyze the trends of human schistosomiasis prevalence in Hubei Province from 2004 to 2018, so as to provide the evidence for formulating the schistosomiasis elimination strategy in the province. METHODS: All data pertaining to human schistosomiasis prevalence in Hubei Province were collected from 2004 to 2018, and the trends for changes in seroprevalence, egg-positive rate and prevalence of human Schistosoma japonicum infection were analyzed using a Joinpoint regression model. RESULTS: Both of the numbers of residents seropositive and egg-positive for S. japonicum infections appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the prevalence of human S. japonicum infections reduced from 6.85% in 2004 to 0 in 2018. Joinpoint regression analysis showed that the prevalence of human S. japonicum infections appeared an overall tendency towards a reduction in Hubei Province from 2004 to 2018 [average annual percent change (AAPC) = -24.1%, P < 0.01], and the trends for the reduction were both significant during the period from 2004 to 2006 [annual percent change (APC) = -35.1%, P < 0.01] and from 2006 to 2018 (APC = -22.1%, P < 0.01). The prevalence of human S. japonicum infections appeared a tendency towards a decline in islet (AAPC = -25.1%, P < 0.01), inner embankment (AAPC = -26.4%, P < 0.01) and hilly subtypes of schistosomiasis-endemic areas (AAPC = -32.5%, P < 0.01) of Hubei Province from 2004 to 2018, and the prevalence all appeared a tendency towards a decline during the infection control stage (from 2004 to 2008), the transmission control stage (from 2009 to 2013) and the transmission interruption stage (from 2014 to 2018) (AAPC = -28.0%, -24.4% and -63.8%, all P values < 0.01). The seroprevalence of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = -14.5%, P < 0.01), and the trends for the reduction were both significant during the period from 2004 to 2012 (APC = -8.4%, P < 0.01) and from 2012 to 2018 (APC = -22.1%, P < 0.01). In addition, the egg-positive rate of human S. japonicum infections appeared an overall tendency towards a decline in Hubei Province from 2004 to 2018 (AAPC = -30.6%, P < 0.05), and the trend for the reduction was significant during the period from 2007 to 2014 (APC = -15.5%, P < 0.01). CONCLUSIONS: The prevalence of human schistosomiasis appeared a tendency towards a decline in Hubei Province from 2004 to 2018, and the islet and inner embankment subtypes of endemic areas are a high priority for schistosomiasis control during the stage moving towards elimination in Hubei Province.

[Effectiveness and safety of robotic assisted-bronchoscopy system in locating and removing spring coils placed in the peripheral lung of beagle dogs: a pilot study].

Objective: To evaluate the effectiveness and safety of the robotic assisted bronchoscope system for localizing and removing the spring coils that placed in the peripheral lung of beagle dogs. Methods: The study was conducted from June 18th to June 20th, 2021. Metallic lung coils were placed as the simulated lesions to the periphery of the lungs of two adult male beagle dogs using a bronchoscope under general anesthesia. The navigation path was planned by the navigation function that built in the robotic bronchoscope system. After training, the doctors operated the robotic bronchoscope system to locate and remove the coils from the lung. The navigation success rate, sampling success rate, position of the coil, navigation time, sampling time, and operation time were evaluated. The damage to the airway mucosa during the operation and the vital signs of the beagles during and post-operation were accessed. Chest computerized tomography (CT) was performed post-operation to detect if there were complications such as pneumothorax and bleeding. Results: A total of 12 spring coils were successfully inserted into the two beagles. All the navigation paths of the simulated lesions were successfully planned. The navigation success rate was 12/12. The navigation time was (43.9±19.8) seconds. The distance between the tip of the flexible endoscope arm and the target point measured by the navigation system was (6.93±2.15) mm. The locations of the simulated lesions were distributed in the 6th-8th generation of bronchi. The sampling success rate was 12/12. The sampling time was (42.4±11.3) seconds. There was no pneumothorax or mediastinal emphysema after the placement of the coil. The vital signs of the beagle dogs were stable throughout the operation, and no operation-related or postoperative complications occurred. Conclusions: The robotic bronchoscope system can be used to locate and remove the spring coils from the peripheral lung of beagle dogs, and the procedure is simple and safe. It suggests that the robotic bronchoscopy system has great clinical significance in the sampling and diagnosis of peripheral lung lesions.

[Establishment of an indicator system for schistosomiasis transmission risk assessment after transmission interruption in Hubei Province based on the Delphi method].

OBJECTIVE: To establish an indicator system for assessment of schistosomiasis transmission risk after transmission interruption in Hubei Province, so as to provide insights into the precise control of schistosomiasis. METHODS: The indicator system was preliminarily established based on data collection, literature review, expert interviews. Two rounds of expert consultation were performed. The indicator system was screened based on the importance, operability, sensitivity and comprehensive score of the indicators, and the weights of each indicator were calculated. The credibility of the Delphi method was evaluated by calculating the active coefficient of the experts, degree of expert authority and coordination levels of experts' opinions. RESULTS: An indicator system for assessment of schistosomiasis transmission risk was preliminarily established, including 3 primary indicators, 12 secondary indicators and 44 tertiary indicators. A Delphi consultation was performed among 17 experts participating in schistosomiasis control, management and research. Following two rounds of consultation, a risk assessment indicator system was finally constructed, including 3 primary indicators, 10 secondary indicators and 35 tertiary indicators. Among the primary indicators, the variable with the highest normalized weight was the current status of schistosomiasis (0.420 2), followed by social factors (0.397 3) and natural environments (0.182 5). Among the secondary indicators, those with high combined weights included risk monitoring (0.142 3), current snail status (0.140 1), and current prevalence of human and livestock infections (0.137 8). Among the tertiary indicators, those with high combined weights included the positive rate of wild feces (0.049 8), the prevalence of snail infections (0.047 4), and the area of snail habitats submerged by floods (0.046 8). During the two-round consultation, the active coefficients of the experts were 85.00% and 100.00%, the degree of expert authority was both 0.75 and greater, and the coordination levels of experts' opinions were 0.405 to 0.521 and 0.592 to 0.695 (all P values < 0.05). CONCLUSIONS: An indicator system for assessment of schistosomiasis transmission risk is successfully established after transmission interruption in Hubei Province based on the Delphi method, which provides insights into the identification of the schistosomiasis transmission risk and the targets for schistosomiasis control in Hubei Province.

[The influence of peripheral blood sample storage and delivery on the quantitative detection result of BCR-ABL (P210) transcript levels].

Objective: To explore the influence of storage and delivery conditions of the peripheral blood samples from patients with chronic myeloid leukemia (CML) on the real-time quantitative PCR (RQ-PCR) detection of the BCR-ABL (P210) transcript levels. Methods: The peripheral blood samples of 84 CML patients were collected. The same sample was divided into different groups according to storage time (0, 6, 12, 24, 48, and 72 h) , temperature (room temperature, 18-24 ℃; low temperature, 2-8 ℃) , and vibration conditions (3, 6, and 12 h) . RQ-PCR was used to detect BCR-ABL (P210) transcript levels of the different groups. This study logarithmically transformed (log(10N)) the original data [BCR-ABL copy number, ABL copy number, and BCR-ABL (P210) transcript levels]. Results: ①Agarose gel electrophoresis showed significant RNA degradation of samples after storage for 48 and 72 h at room temperature. ②Among the overall samples, the BCR-ABL copy number of the samples stored at room temperature for 48 and 72 h was significantly lower than that of the samples stored at low temperature (P<0.05) . However, the BCR-ABL (P210) transcript levels had no significant difference between samples stored at low temperature and room temperature. ③No significant changes were noted in the BCR-ABL (P210) transcript levels at different storage times (6, 12, 24, 48, and 72 h) regardless of storage temperature (P>0.05) compared with that at baseline (0 h, -0.56±1.51) . ④ The BCR-ABL copy number of the overall sample only decreased significantly (P<0.05) at 48 h (2.93±1.59) and 72 h (2.79±1.42) compared with that at baseline (0 h, 3.35±1.60) when stored at room temperature. The ABL copy number in the overall sample decreased significantly at 48 and 72 h (whether low and room temperature; P<0.05) . However, no significant changes were noted in the BCR-ABL (P210) transcript levels after vibration for 3 h (-1.29±1.81) , 6 h (-1.24±1.72) , and 12 h (-1.18±1.68; P>0.05) compared with that at baseline (0 h, -0.60±1.37) . Conclusion: Sample storage time, storage temperature, and vibration can interfere with the results of BCR-ABL and ABL copy number but have no significant effect on the quantitative determination of BCR-ABL (P210) transcript levels. This study provides strong support for the feasibility of transregional transportation of peripheral blood samples from patients with CML.

[Risk analysis for hepatocellular carcinoma in patients with chronic hepatitis B-associated cirrhosis complicated by type 2 diabetes mellitus: a 5-year prospective cohort study].

OBJECTIVE: To elucidate the risk and synergistic factors of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B-associated cirrhosis (CHB-Cir) complicated by type 2 diabetes (T2DM). OBJECTIVE: The patients with CHB-Cir who were followed up in Hepatology Center of Nanfang Hospital from June 2010 to June 2019 were divided based on their T2DM status into two cohorts matched for gender, age, HBeAg status and HBV DNA load: CHB-Cir with T2DM group (observation group) and CHB-Cir without T2DM group (control group). All the patients were followed up at a 6-month interval, and the cases with complete clinical data and follow-up data for more than 2 years were included in the analysis. Kaplan- Meier method was used to compare the cumulative incidence of HCC between the two groups. A Cox proportional hazard regression model was used to analyze the relationship between T2DM and the risk of HCC in these patients. OBJECTIVE: A total of 467 patients with a mean follow-up time of 4.4±1.62 years were included in the analysis, including 203 in the observation group and 264 in the control group. Sixty-nine and forty-eight new HCC cases occurred in the observation group and control group, respectively, showing a significantly higher incidence rate of HCC in the observation group (P < 0.001). The cumulative incidence of HCC in the observation group was significantly higher than that in the control group (P < 0.001), with a relative risk of 2.096 (P < 0.01). After adjustment for age (≥40 years), family history of liver cancer, previous antiviral therapy, elevated cholesterol and elevated LDL cholesterol, T2DM remained an independent risk factor for HCC in CHB-Cir patients (P=0.000). OBJECTIVE: T2DM is an independent risk factor for HCC, and the risk of HCC increases by more than two folds in CHB-Cir patients complicated by T2DM, suggesting the clinical significance of early interventions of diabetes to reduce the risk of HCC in CHB-Cir patients.

Encapsulation of bacterial cells in cytoprotective ZIF-90 crystals as living composites.

Exploiting metal-organic frameworks (MOFs) as selectively permeable shelters for encapsulating engineered cells to form hybrid living materials has attracted increasing attention in recent years. Optimizing the synthesis process to improve encapsulation efficiency (EE) is critical for further technological development and applications. Here, using ZIF-90 and genetically engineered Escherichia coli (E. coli) as a demo, we fabricated E. coli@ZIF-90 living composites in which E. coli cells were encapsulated in ZIF-90 crystals. We illustrated that ZIF-90 could serve as a protective porous cage for cells to shield against toxic bactericides including benzaldehyde, cinnamaldehyde, and kanamycin. Notably, the E. coli cells remained alive and could self-reproduce after removing the ZIF-90 crystal cages in ethylenediaminetetraacetic acid, suggesting a feasible route for protecting and prolonging the lifespan of bacterial cells. Moreover, an aqueous multiple-step deposition approach was developed to improve EE of the E. coli@ZIF-90 composites: the EE increased to 61.9 ± 5.2%, in contrast with the efficiency of the traditional method (21.3 ± 4.4%) prepared with PBS buffer. In short, we develop a simple yet viable strategy to manufacture MOF-based living hybrid materials that promise new applications across diverse fields.

Vitamin D receptor alleviates hepatic ischemia and reperfucion injury by mediating endoplasmic reticulum stress through autophagy.

Hepatic ischemia and reperfusion (IR) injury is a common complication in clinical practice. Endoplasmic reticulum (ER) stress and autophagy are the key factors in the process of hepatic IR injury. The vitamin D receptor (VDR) can mediate ER stress and autophagy; however, it can also mitigate IR injury. The relationship between VDR, ER stress, and autophagy in hepatic IR injury is unknown. VDR knockout mice and wild-type littermates underwent 70% liver ischemia (90 min) and reperfusion (6 h). To observe the effect of autophagy in the relationship with VDR and ER stress in hepatic IR injury, the autophagy agonist rapamycin and its inhibitor chloroquine were used in the study. Meanwhile, RAW264.7 cells were studied in vitro to verify the relationship between VDR, autophagy, and ER stress. VDR was involved in hepatic IR injury and its activation reduced liver injury and inhibited an inflammatory response. ER stress took part in the liver injury during the process of IR. Meanwhile, VDR activation was found to inhibit inflammation by ER stress, and vice versa. Furthermore, autophagy was the connection between VDR and ER stress. After treatment with rapamycin or chloroquine, the effect of VDR activation or VDR silencing in ER stress was partially reversed. The same tendency was observed in vitro. ER stress and autophagy are important mechanisms of hepatic IR injury. VDR can regulate ER stress through autophagy and then protect the liver from IR injury.

[Survey of snail distribution in Four-lake Basin of Hubei Province].

OBJECTIVE: To investigate the distribution of Oncomelania snails in Four-Lake Basin of Hubei Province, so as to provide scientific evidence for the development of snail control interventions. METHODS: The snail distribution was surveyed by means of the retrospective study and cross-sectional survey in the Four-Lake Basin in Spring of 2016. The data pertaining to the endemic situation of schistosomiasis were collected and analyzed in the Four-Lake Basin from 2008 to 2018, and the associations of snail habitat areas with the prevalence of Schistosoma japonicum in humans and bovines were examined. RESULTS: There were 16 003 snail habitats in the 9 schistosomiasis-endemic counties (districts) in the Four-Lake Basin in 2016, covering an area of 246 million m2. The mean density of living snails was 0.622 5 snails/0.1 m2, which was relatively high in weed-type settings (0.688 0 snails/0.1 m2) and ditches (0.706 4 snails/0.1 m2). Type I (current snail habitats, 53.03%) and Ⅱ- Ⅳ (historical snail habitats, 46.97%) settings were predominant snail habitats. A big change was seen in snail habitats in dry farmland, marshland and paddy farmland, and environmental modification resulted in satisfactory snail control effectiveness. In addition, the area of snail habitats positively correlated with the changes in the prevalence of S. japonicum infections in humans (r = 0.842, P < 0.01) and livestock (r = 0.695, P < 0.01). CONCLUSIONS: The integrate strategy with an emphasis on the control of the source of S. japonicum infections results in remarkable snail control effectiveness in the Four-Lake Basin; however, there is a risk of re-emerging snail habitats.

Downregulation of CDCA3 expression inhibits tumor formation in pancreatic cancer.

Downregulation of cell division cycle-associated 3 (CDCA3) markedly inhibited cell growth and induced apoptosis in tumors. However, the effect of CDCA3 in pancreatic cancer (PAC) was rarely investigated. Therefore, this study attempted to clarify the role of CDCA3 in PAC. The mRNA and protein expression of CDCA3 were examined in PAC cell lines and tumor tissues by using real-time quantitative PCR (RT-qPCR), western blotting (WB), and immunohistochemistry (IHC). The effects of CDCA3 downregulation on cell proliferation, apoptosis, and colony information were investigated through MTT assay, Annexin V-APC single staining cell apoptosis detection, and colony formation test. The microarray and ingenuity pathway analysis were employed to explore the potential regulatory relation. The tumor xenograft model was established for determining the effect of CDCA3 downregulation on the growth of PAC in vivo. The results showed that the expression of CDCA3 in tumor tissues was higher than that of normal tissues (p<0.05). In addition, the mRNA expression of CDCA3 was markedly increased in PANC-1 cells and SW 1990 cells when compared with human pancreatic duct epithelial (HPDE) cells (p<0.05). MTT assay showed that the cell proliferation of PANC-1 cells and SW 1990 cells was significantly inhibited after the lentivirus transfection of CDCA3 knockdown (p<0.05). Annexin V-APC apoptosis assays suggested that the apoptotic cell number was markedly increased in the shCDCA3 group compared to that in the shCtrl group in SW 1990 cells and PANC-1 cells (p<0.05). Meanwhile, the activity of caspase-3/7 was obviously elevated in the shCDCA3 group compared to the shCtrl group (p<0.05). The colony formation was notably inhibited in the shCDCA3 group relative to the shCtrl group in SW 1990 cells (p<0.05). Moreover, the tumor growth was evidently suppressed in the shCDCA3 group compared with the shCtrl group in vivo (p<0.05). These findings revealed that CDCA3 plays a crucial role in the progress of PCA by regulating cell apoptosis and proliferation, which may serve as a potential target for PAC treatment.