Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter micro-tubule associated homolog 2(JPT2)is a critical molecule in Ca2+mobilization,and its intrinsic mecha-nism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and theJPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca2+mobilization.Tran-scriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the produc-tion of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and in-flammatory polarization via JPT2/PI3K/AKT signaling.

The damage caused by space microgravity environment to the body systems of astronauts directly affects their work efficiency.This paper reviewed previous studies on the effects of space microgravity environment and ground simulated microgravity environment on cognition and emotion, potential mechanisms and interventions. It was found that a microgravity environment led to dysfunction in learning, memory, spatial orientation and other aspects, and caused anxiety and depression. The mechanisms of cognitive and emotional impairment associated with microgravity environment are complex, including neuronal damage, brain structure changes, neurotransmitter disorders, synaptic dysfunction, oxidative stress injury, and energy metabolism disorders. Pharmacological approaches such as natural extracts, physical interventions such as repetitive transcranial magnetic stimulation, and new therapies such as probiotics were expected to reduce cognitive impairment and mood disorders caused by microgravity exposure. With the development of aerospace medicine in China, the potential mechanism and interventions of microgravity environment on cognitive and emotional impairment remain to be further studied.

Objective:To evaluate the clinical value of nanopore targeted sequencing (NTS) in pathogens detection in urinary tract by comparing the results of different tests performed on the same urine sample.Methods:The results of NTS and urine culture test collected from 326 patients in the Department of Urology of People's Hospital of Wuhan University from July 2020 to June 2021 were retrospectively analyzed. There were 224 males and 102 females. The average age was (56.88 ± 14.58)years old. χ 2 test and Student’s test and Wilcoxon's sign rank test were used to analyze the differences of the pathogen detection rate, pathogen types results and detection time consuming between NTS and urine culture. The clinical value of the NTS in rapid detection of urinary pathogens was evaluated. Results:Among 326 hospitalized patients, the urinary tract microbes’ detecting rate of NTS was significantly higher than that of urine culture[67.80%(221/326)vs. 23.93%(78/326), χ2=130.25, P<0.01]. The uropathogens detecting rate of NTS was significantly higher than that of urine culture[54.29%(177/326)vs. 23.31%(76/326), χ2=38.95, P<0.01]. The number of urinary tract microbes detected by NTS was significantly higher than that of urine culture ( Z=11.49, P<0.01), the number of uropathogens was significantly higher than that of urine culture ( Z=9.67, P<0.01). The detection time of NTS and urine culture positive samples was (24.29±2.65) h and (49.28±11.30) h, the difference was statistically significant ( t =39.48, P<0.01). The results obtained by using NTS and urine culture were consistent in 135 (41.41%) samples. In 150 (46.01%) samples, NTS could detect the urinary tract microbes while urine culture cannot find, of which 112 cases (34.36%) were uropathogenic. In 27 cases (8.28%), more pathogens were detected by NTS except those from urine culture. In 6 cases (1.84%) re-detecting NTS after antibiotic therapy, the number of reads of primary uropathogen decreased gradually with the growth of colonizing bacteria or opportunistic pathogens appeared in the end. Re-examinations of urine culture could verify the results of NTS detection on admission in 5 cases (1.53%). NTS in 2 cases (0.61%) could cover the uropathogens of subsequent several urine cultures. Conclusions:NTS has the advantages of rapid, sensitive and comprehensive detection of urinary tract infection pathogens. When urine culture is not yet reported or even negative, NTS already has a certain clinical reference value and can be used as an effective supplement to urine culture, which is conducive to the comprehensive judgment of the patient's condition.

【Objective】 To investigate the effects of miR-126-3p targeting chemokine receptor 1 (CCR1) in exosomes derived from bone marrow mesenchymal stem cells (BMSC) on the proliferation, migration, and invasion of lung cancer cells. 【Methods】 BMSC cells were cultured; exosomes were extracted and identified by the exosomal marker proteins CD63 and TSG101. After exosome culture of A549 cells for different durations (0, 24, 48, and 72 h), cell survival rate was detected by CCK-8, mRNA levels of miR-126-3p and CCR1 were detected by qRT-PCR, and cell migration and invasion abilities were detected by Transwell assay. The relative expressions of CCR1, epithelial cadherin (E-cad), neural cadherin (N-cadherin), and Vimentin were detected by Western blotting. 【Results】 Exosomes had round or oval cup-shaped structures with bright edges and dark middle, with a particle size distribution of about 152 nm, expressing CD63 and TSG101 proteins. The expression of miR-126-3p in exosomes was higher than that in A549 cells. The expression of miR-126-3p was low in A549 cells and that of CCR1 mRNA was high. However, after co-culture with exosomes, the expression of miR-126-3p in A549 cells was increased, while the expression of CCR1 was decreased. A549 cells were cocultured with exosomes for 0, 24, 48, and 72 h. The survival rate, migration and invasion abilities, CCR1 gene and protein expression levels, and N-cad and Vimentin protein expression levels of A549 cells decreased gradually with the extension of culture time. The level of miR-126-3p and the expression of E-cad protein increased gradually with the extension of culture time. 【Conclusion】 The co-culture of exosomes derived from bone marrow mesenchymal stem cells with A549 cells can increase the expression level of miR-126-3p, and miR-126-3p can reduce the proliferation, migration, and invasion of A549 cells by targeting the inhibition of CCR1 expression.

Objective:To compare the performance and surgical outcomes of domestic single-use digital flexible ureteroscopes with reusable digital flexible ureteroscopes in treatment of upper urinary stones.Methods:A prospective, single-blind, multicenter and randomized controlled study was performed from September 2018 to June 2019. Eligible patients were randomly assigned, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-75 years, solitary upper urinary stone with stone size between 0.8 and 2.0 cm and CT value less than 1 400 HU, negative preoperative urine culture and normal renal function. Exclusion criteria included: patients with acute urinary tract infection, intransitable urethral strictures, impassable ureteropelvic junction obstructions, systemic hemorrhagic disease, coagulation function abnormalities or bleeding tendency, severe hypertension or cardiopulmonary insufficiency, severe hip malformation and difficulty in meeting the demand of operation position and pregnant and lactation women. The device used in the experimental group was a domestic single-use digital flexible ureteroscope, and the device used in the control group was an imported Olympus digital flexible ureteroscope. The qualified rate of clinical comprehensive evaluation (including image quality and operational performance), the rate of device failure, the stone-free rate and the occurrence rate of adverse events (including increase in urine red blood cell and white blood cell counts, postoperative hematuria, nausea, vomiting, dizziness, and fever) in the two groups were recorded.Results:A total of 186 eligible study cases were collected from the People's Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University, and the First Affiliated Hospital of Guangzhou Medical University. 90 cases in the final experimental group and 88 cases in the control group completed the trial and were included in the evaluation. There were no statistically significant differences among age [(48.40±11.36) vs. (47.40±12.53)years old, P=0.594], male to female ratio (62/28 vs. 56/32, P =0.874), BMI [(24.8±2.1) kg/m 2 vs. (25.1±2.0)kg/m 2,P =0.331], hydronephrosis (no/slight vs. mild/severe) (62/28 vs. 65/23, P =0.874), stone location and stone size [(12.8±4.7) mm vs. (11.9±5.2) mm, P =0.227]. There were no significant differences in terms of qualified rate of clinical comprehensive evaluation [98.9% (89/90) vs. 100.0% (88/88), P =0.991], lithotripsy success rate [84.4% (76/90) vs. 84.1% (74/88), P =0.888], device failure/defect rate (both 0%), and the incidence of adverse events [50.0% (45/90) vs. 52.0% (51/88), P =0.894]. The highest incidence of adverse events in two groups was the increase of red blood cells and white blood cells of routine urine after operation. There was no serious adverse event in the experimental group and 1 serious adverse event in the control group. Conclusions:There was no significant difference in image quality, device failure/defect rate, lithotripsy success rate, and adverse event rate between single-use digital flexible ureteroscopes and reusable digital flexible ureteroscopes for lithotripsy of upper ureteral and pelvic stones. Domestic single-use digital flexible ureteroscopes have good safety and effectiveness in the treatment and microscopy of upper urinary tract stones.

Objective:To investigate the effects of Bifidobacterium animalis subsp. lactis BB-12 on hippocampal neuroinflammation and cognitive function of mice after whole brain radiotherapy. Methods:A total of sixty male C57BL/6J mice aged 7-8 weeks were randomly divided into 5 groups with 12 mice in each group: control group (Con group), probiotic group (BB-12 group), irradiation group (IR group), irradiation and Memantine group (IR+ Memantine group), irradiation and probiotic group (IR+ BB-12 group). The model of radiation-induced brain injury of mice was established by 10 Gy whole brain radiotherapy with a medical linear accelerator. Y-maze test was used to evaluate the cognitive function. The activation of microglia and astrocytes was observed by immunofluorescence staining. The expressions of inflammatory cytokines interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) were detected by quantitative real-time reverse transcription polymerase chain reaction (QRT-PCR) and Western blot.Results:Y-maze test showed that, compared with Con group, the percentage of the times of reaching the novel arm in the total times of the three arms decreased significantly in the IR group ( t=5.04, P<0.05). BB-12 mitigated radiation-induced cognitive dysfunction ( t=4.72, P<0.05). Compared with Con group, the number ( t=3.05, 7.18, P<0.05) and circularity index ( t=6.23, 2.52, P<0.05) of Iba1 and GFAP positive cells were increased, the microglia and astrocytes were activated in the hippocampus of IR group, but these alterations were eliminated by BB-12. After whole brain IR, the mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6 and TNF-α in the hippocampus of mice were significantly increased compared with Con group ( tmRNA =4.10, 3.04, 4.18, P<0.05; tprotein=11.49, 7.04, 8.42, P<0.05), which were also significantly reduced by BB-12 compared with IR group ( tmRNA=4.20, 3.40, 2.84, P<0.05; tprotein=6.36, 4.03, 3.75, P<0.05). Conclusions:Bifidobacterium animalis BB-12 can suppress neuroinflammation mediated by microglia and astrocytes in the hippocampus of mice after radiotherapy and alleviates IR-induced cognitive dysfunction. Therefore, BB-12 has potential application in alleviating radiation induced brain injury.

Objective:To investigate the availability and safety of a domestic disposable digital flexible cystoscope compared with a reusable Olympus digital flexible cystoscope in cystoscopy and removal of double J stent.Methods:From August 2018 to March 2019, patients were enrolled in this prospective, open, multicenter, randomized, parallel positive controlled clinical trial study, which were from department of Urology in Renmin Hospital of Wuhan University, the First Affiliated Hospital of Xiamen University and the First Affiliated Hospital of Guangzhou Medical University. The experimental group and control group were assigned into a 1∶1 ratio by random table method. Inclusion criteria included age≥18 years and have indications for cystoscopy or removal of double J stent. Exclusion criteria included patients having acute genitourinary tract infection, having tuberculous bladder contracture, bladder capacity less than 50ml, having urethrostenosis, female menstrual period, pregnancy and lactation, having difficulty for lithotomy position, having serious cardio-cerebrovascular disease and liver or kidney dysfunction. A domestic disposable digital flexible cystoscope was adopted in the experimental group, whereas a reusable Olympus digital flexible cystoscope was used in the control group. Acceptability of image was defined as primary availability indicator, while success rate of working and performance score were defined as secondary availability indicators and mean operating time was calculated for cystoscopy only and cystoscopy plus removal of double J stent respectively, yet rate of adverse event as well as rate of equipment defects were sorted as safety indicators.Results:A total of 188 cases which were listed in per protocol set completed the clinical trial study successfully. There were 95 cases in the experimental group and 93 cases in the control group. Acceptability of image was 93.68%(89/95) and 96.77%(90/93) respectively in two groups( P=0.52). Success rate of working was 100.00%(95/95) and 98.92%(92/93) respectively in two groups ( P=0.49). Performance score was 14.41±0.93 and 14.56±0.84 respectively in two groups ( P=0.23). Mean operating time (MOT) only for cystoscopy was (15.3±2.6) min and (15.4±3.3)min respectively in two groups ( P=0.93), while MOT for cystoscopy plus removal of double J stent was (21.0±3.2) min and (21.7±3.9) min respectively in two groups ( P=0.69). Rate of adverse event was 8.42%(8/95) and 9.68%(9/93) respectively in two groups( P=0.76). There was no equipment defects in both groups. Conclusions:There is no statistical difference in acceptability of image, success rate of working, performance score, mean operating time for cystoscopy or removal of double J stent, rate of adverse events and rate of equipment defects. A domestic disposable digital flexible cystoscope has shown non-inferiority in the availability and safety compared with a reusable Olympus digital flexible cystoscope.

Triterpenoids are a class of natural products of great commercial value that are widely used in pharmaceutical, health care and cosmetic industries. The biosynthesis of triterpenoids relies on the efficient synthesis of squalene epoxide, which is synthesized from the NADPH dependent oxidation of squalene catalyzed by squalene epoxidase. We screened squalene epoxidases derived from different species, and found the truncated squalene epoxidase from Rattus norvegicus (RnSETC) showed the highest activity in engineered Escherichia coli. Further examination of the effect of endogenous cytochrome P450 reductase like (CPRL) proteins showed that overexpression of NADH: quinone oxidoreductase (WrbA) under Lac promoter in a medium-copy number plasmid increased the production of squalene epoxide by nearly 2.5 folds. These results demonstrated that the constructed pathway led to the production of squalene epoxide, an important precursor for the biosynthesis of triterpenoids.
Animals ; Escherichia coli/genetics* ; NADPH-Ferrihemoprotein Reductase ; Protein Engineering ; Rats ; Repressor Proteins ; Squalene ; Squalene Monooxygenase/genetics*

Objective:To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province.Methods:Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information.Results:As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure.The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend χ2=2.20, P<0.05) and fatigue (trend χ2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend ( H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage ( F=51.65, P<0.01), but the intervals between disease onset and hospital visit ( F=5.32, P<0.01), disease onset and diagnosis ( F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number ( R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions:The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests. the early screening cannot only depend on body temperature monitoring.

Objective: To analyze the epidemiological and spatial-temporal distribution of Brucellosis, epidemic encephalitis B and hemorrhagic fever with renal syndrome (HFRS) in Gansu province during 2014-2018 so as to provide evidence for the prevention and control of those diseases. Methods: A database was established in Gansu province from 2014 to 2018, using the geographical information system. A spatial distribution map was drawn, with trend analysis and space-time clustering used to study the 3-dimention of the diseases, by using both ArcGIS 10.5 and SaTScan 9.6 softwares. Results: Results from the trend surface analysis showed that the incidence of Brucellosis decreased gradually from north to south parts while the U type curve could reflect the distribution from the east to the west areas. Incidence of epidemic encephalitis B decreased significantly from south to north areas in the province, with incidence higher in the eastern than in the mid-west region. Difference on the incidence of HFRS was not significantly visible in the eastern and western regions, while the incidence was slightly higher in the southern than the northern parts of the province. Spatial and space-time clustering did exist among the 3 diseases in Gansu from 2014 to 2018. The areas with clusters of Brucellosis appeared in the eastern parts during 2014-2015, including 19 counties. The areas with secondary clusters of Brucellosis were seen in the Hexi district, including 4 counties, during 2017-2018. The areas with high incidence of epidemic encephalitis B were clustered in the middle and southeast areas, including 32 counties, during 2017-2018. Areas with most clusters of HFRS appeared in Min county of Dingxi city in 2018, with the areas of secondary clusters in 8 counties of the eastern areas in 2018. Conclusions The overall incidence rates of the 3 natural focus diseases were in a upward trend and showing obvious characteristics on spatial clustering. According to the distributive characteristics, effective measures should be developed accordingly.