Objective To investigate the correlation of solute carrier protein 17 family member 1 (SLC17A1) gene single nucleotide polymorphisms (SNPs) and susceptibility to hyperuricemia (HUA) in automotive manufacturing workers. Methods A total of 192 Han male workers diagnosed with HUA were selected as the case group, 192 Han male workers without HUA from the same enterprises were selected as the control group. These workers were determined by the matching factor of age, total length of service, and body mass index by the 1∶1 case-control study method. Peripheral venous blood from the workers was collected for DNA extraction. Two SNPs of SLC17A1 were genotyped by MassArray system. Results The gene frequency distributions of SLC17A1 rs2096386 and rs1183201 of workers in the control group were in consistent with the Hardy-Weinberg equilibrium test (both P>0.05). The allele frequency distribution of rs2096386, and the genotype and allele frequency distribution of rs1183201 were significantly different between workers in the two groups (all P<0.05). There was no significant difference in genotype frequency distribution of rs2096386 between workers in the two groups (P>0.05). The results of conditional logistic regression analysis showed that workers with G allele at rs2096386 increased the risk of HUA [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.01-2.04], workers with T allele at rs1183201 increased the risk of HUA (OR=2.03, 95%CI =1.29-3.19), after adjusting for confounding factors such as serum creatinine, blood urea nitrogen, alanin aminotransferase and aspartate aminotransferase. While workers with TA and TA+AA genotypes at rs1183201 had a lower risk of HUA than those with TT genotype (OR=0.51, 95%CI =0.30-0.85; OR=0.50, 95%CI =0.30-0.83), workers with TA genotype at rs1183201 had a lower risk of HUA than those with TT+AA genotype (OR=0.53, 95%CI =0.32-0.88). Conclusion The polymorphisms at rs2096386 and rs1183201 of SLC17A1 gene may be correlated with HUA susceptibility among automobile manufacturing workers in Guangzhou City.

OBJECTIVES: To explore the expression profile of circular RNAs (circRNAs) and their potential roles in prognosis and progression of Wilms' tumor (WT). METHODS: Four pairs of WT and adjacent tissues were collected for high-throughput circRNA sequencing to identify the differentially expressed circular RNAs. RT-qPCR was used to verify the expression levels of the top 6 candidate circRNAs in the clinical samples. hsa_circ_0001900 was selected for analysis of its correlation with clinicopathological features and prognosis in 34 patients with WT. Sanger sequencing and RNase R digestion experiments were used to verify the cycling site and structural stability of hsa_circ_0001900 molecule. RESULTS: A total of 23 978 circular RNA molecules were identified in WT tissues by high-throughput circular RNA sequencing, and among them 614 were differentially expressed in WT. hsa_circ_0001900 showed the highest expression level among the differentially expressed circRNAs, which was consistent with the findings in clinical tumor samples and the sequencing results. Correlation analysis showed that hsa_circ_0001900 expression level was positively correlated with WT volume, and the children with high hsa_circ_0001900 expression had a lowered recurrence-free survival rate. The results of Sanger sequencing verified the circular splice site sequence of the molecule, and Rnase R digestion assay confirmed its stable covalent structure. CONCLUSIONS This study presents a comprehensive expression profile of circular RNAs in WT, and the expression level of hsa_circ_0001900 is related to the size of WT and the patients' prognosis, suggesting its possible role as a key driving gene in WT progression.
Humans ; RNA, Circular ; Wilms Tumor/pathology* ; Prognosis ; High-Throughput Nucleotide Sequencing ; Kidney Neoplasms/genetics* ; Sequence Analysis, RNA ; Male ; Female

Objective:To analyze the clinic effects of arthroscopic partial trapeziectomy and suture button suspensionplasty in the treatment of first carpometacarpal joint (CMCJ) Eaton stage II/III arthrosis.Methods:A retrospective study was conducted on a total of 15 cases (16 hands) of patients including 5 males (1 bilateral) and 10 females with CMCJ stage II/III arthrosis who underwent surgical treatment at the first affiliated hospital of Shenzhen university from January 2020 to June 2022, with mean age of 56.7±6.4 years (range, 46-75 years). The duration from pain to treatment was 7.8±3.2 months (range, 4-14 months). X-ray showed narrowing of CMCJ with osteophytes and distal radial subluxation. All the patients were treated with arthroscopic partial trapeziectomy and suture button suspensionplasty. The preoperative and last postoperative follow-up radiographs, visual analogue scale (VAS), thumb's Kapandji scores, disabilies of the arm, shoulder, and hand (DASH) scores, grip and pinch strength and time to return to work were compared.Results:All cases were followed up for 19.6±6.3 months (range, 11-36 months). The postoperative X-ray showed all the CMCJs were reduced with a normal height of first metacarpal. The mean time for patients to return to their daily activities was 18.69±3.70 d and the mean time to return to work was 24.63±4.91 d. The average VAS score decreased from 6.56±1.15 preoperatively to 1.00 (0.75, 1.25). The preoperative Kapandji's score was 8.00±0.82 and the postoperative Kapandji's score was 8.00 (7.25, 9.00). The average DASH values improved from 24.06±3.19 to 4.00 (3.00, 5.00). The were significant differences except for Kapandji score ( Z=-4.905, P<0.001; Z=-0.121, P=0.905; Z=-4.846, P<0.001). The mean grip and pinch strength showed improvement from an average of 16.4 (14.13, 18.68) kg and 1.70±0.35 kg to 26.14±3.27 kg and 3.58±0.91 kg with significant difference ( Z=-4.617, P<0.001; t=-7.669, P<0.001). Conclusion:Arthroscopic partial trapeziectomy and suture button suspensionplasty is a minimally invasive surgery for the treatment of first CMCJ Eaton stage II/III arthrosis. By this technique, the patients' existing instability and pain problems can be solved.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.

Objective To explore the value of combined detection of cerebrospinal fluid lactate (LA), interleukin-27 (IL-27) and interferon-γ (IFN-γ) in diagnosing bacterial meningitis after neurosurgical operation in Intensive Care Unit (ICU). Methods A total of 54 patients with bacterial meningitis after neurosurgical operation in ICU were collected as disease group, and 62 patients without bacterial meningitis after operation were collected as control group. Fully automated biochemical analyzer and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of LA, IL-27 and IFN-γ in cerebrospinal fluid; the Logistic regression model was used to analyze the related factors affecting bacterial meningitis after operation; the receiver operating characteristic (ROC) curve was used to analyze the diagnostic values of LA, IL-27 and IFN-γ in cerebrospinal fluid for bacterial meningitis after operation. Results The glucose level in the disease group was significantly lower than that in the control group, while the white blood cell count and protein level were significantly higher than those in the control group (P < 0.01). The expression levels of LA and IL-27 in the cerebrospinal fluid in the disease group were significantly higher than those in the control group, while IFN-γ level in the cerebrospinal fluid was significantly lower than that in the control group (P < 0.01). Logistic regression analysis showed that LA, IL-27 and IFN-γ in the cerebrospinal fluid were the influencing factors of bacterial meningitis after neurosurgical operation in ICU (P < 0.05). The area under the curve (AUC) of LA combined with IL-27 and IFN-γ in cerebrospinal fluid in the diagnosis of bacterial meningitis after neurosurgical operation in ICU was 0.955, which was better than that of single diagnosis based on LA (AUC=0.806, Z=4.029, P < 0.001), IL-27 (AUC=0.858, Z=2.513, P=0.012) and IFN-γ (AUC=0.815, Z=3.680, P < 0.001) in cerebrospinal fluid, and the sensitivity and specificity of the combined diagnosis were 87.04% and 93.55% respectively. Conclusion The expression levels of LA and IL-27 in the cerebrospinal fluid of patients with bacterial meningitis after neurosurgical operation in ICU increase significantly, while the expression level of IFN-γ in the cerebrospinal fluid is significantly lower. The combined detection of three indicators has higher diagnostic value for postoperative bacterial meningitis compared with single detection.

Objective To analyze the NBS-LRR disease resistance gene family of Codonopsis pilosula(Franch.)Nannf.and explore the disease resistance mechanism,so as to solve the problem of root rot disease of C.pilosula and promote the breeding and industrial development of C.pilosula.Methods Based on the transcriptome data of C.pilosula in response to root rot pathogen,gene structure,phylogeny,gene interaction and expression pattern of C.pilosula NBS-LRR family genes were analyzed by using bioinformatics methods.Results 88 NBS-LRR family genes were successfully identified.Including N,NL,CN,CNL,TN,TNL and PN,there are 50,14,1,14,4,3 and 2 genes respectively.Their physical and chemical properties,gene structure,phylogeny,gene interaction and expression pattern were analyzed.The results showed that CNL subfamily genes of C.pilosula were amplified during evolution;CNL and TNL gene structures ar-relatively conservative;Expression pattern analysis showed that there were differences in temporal expression patterns of C.pilosula NBS-LRR family genes under F.oxysporum infection.The highly expressed genes DN64786c1g6,DN64786c1g5,DN48234c0g2,DN54844c1g2,DN59747c0g3,DN56071c1g8,DN64591c1g1,DN48464c1g1,DN59886c0g1 play an important role in regulating the disease resistance of C.pilosula.The DN54844c1g2 may interact with GLR family,and then participate in immune regulation by regulating Ca2+ influx;DN64786c1g5 may interact with cytc-1 and cytc-2,and then participate in the response of C.pilosula to root rot by participating in redox reaction;DN59747c0g3 may interact with MPK3 and play an important role in the response of C.pilosula to root rot by participating in map signal cascade,phosphorylating WRKY transcription factor and participating in hypersensitivity reaction(HR).Conclusion The identification and expression analysis of NBS-LRR family genes of C.pilosula is of great significance to explore the mechanism of root rot resistance and gene function of C.pilosula..

Background Previous research indicated that isomers and alternatives of per- and polyfluoroalkyl substances (PFAS) probably disturb glucose metabolism; however, current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent. Besides, studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce. Objective To evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects, as well as identify the key component among population without glucose metabolism problems. Methods We selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China (2015—2016). Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and automatic biochemical analyzer. We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80% participants with fasting blood glucose. Meanwhile, we utilized qgcomp and Bayesian kernel machine regression (BKMR) models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component. Results The average age among the 923 participants in this study was (62.4±13.8) years old, including 472 men (51.1%) and 451 women (48.9%). Among selected PFAS isomers and alternatives, the highest serum concentration was ∑3+4+5m-PFOS (perfluoro-3/4/5-methylheptanesulfonate) with a median concentration of 10.20 ng·mL⁻¹. The concentrations of linear perfluorooctane sulfonate (n-PFOS, 9.61 ng·mL⁻¹), perfluorooctanoic acid (PFOA, 4.55 ng·mL⁻¹), linear perfluorohexane sulfonic acid (n-PFHxS, 2.48 ng·mL⁻¹), 6:2 chlorinated polyfluorinated ethersulfonic acid (6:2 Cl-PFESA, 1.90 ng·mL⁻¹), perfluoro-6-methylheptanesulfonate (iso-PFOS, 1.85 ng·mL⁻¹), perfluorobutanoic acid (PFBA, 1.81 ng·mL⁻¹), perfluorinated n-nonanoic acid (PFNA, 1.39 ng·mL⁻¹), and perfluoro-1-methylheptanesulfonate (1m-PFOS, 1.27 ng·mL⁻¹) were higher than 1.00 ng·mL⁻¹. After being adjusted for selected confounders, PFAS isomers and alternatives were positively associated with fasting blood glucose. With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA, the estimated changes of fasting blood glucose were 0.18 (95%CI: 0.13, 0.23) mmol·L⁻¹ and 0.24 (95%CI: 0.18, 0.30) mmol·L⁻¹, respectively. The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose. The BKMR models reveals that as the quantiles of mixture elevated from the 50^th to the 75^th percentile, the values of fasting blood glucose increased 0.25 (95%CI: 0.21, 0.30) mmol·L⁻¹, and the posterior inclusion probability of PFNA was 0.92, implying that PFNA was the key component. Conclusion PFAS isomers and alternatives are positively associated with fasting blood glucose. PFNA is the key component of the joint association.

Objective:To investigate the effect of long-term chronic ethanol consumption on the spontaneous discharge activity of Purkinje cells in the cerebellar cortex of mice.Methods:Fifty 3-week-old ICR mice, regardless of gender, were divided into control group and ethanol group according to the random number table method, with 25 mice in each group. The mice in ethanol group were administered 20% ethanol (1.6 g/kg, once a day) by gavage, and the control group mice were given the same volume of 0.9% sodium chloride solution by gavage, and the gavage cycle was 28 days.The electrical activity of cerebellar Purkinje cells induced by sensory stimulation was recorded by patch clamp amplifier and data acquisition software. Statistical analysis was conducted by Clampfit 10.3 software and SPSS 22.0 software, t-test and one-way ANOVA were used to compare the data between the two groups and the data before and after intervention of each group. Results:The electrophysiological results showed that the spontaneous simple spike discharge frequency of Purkinje cells in the cerebellar cortex of mice in ethanol group was lower than that of the control group ((26.8±2.5)%, (34.6±4.7)%; t=26.08, P<0.05), and the coefficient of variation was higher than that of the control group ((27.3±3.3)%, (19.2±2.3)%; t=22.95, P<0.05). After cerebral surface perfusion of GABAA receptor antagonist, the frequency of simple peak potentials in the cerebellar cortex of ethanol mice was higher than before administration ( t=10.19, P<0.05), and the coefficient of variation was lower than before administration ( t=28.36, P<0.05). After brain surface perfusion of GABAA receptor antagonist, there was no significant change in the spontaneous simple peak discharge frequency of cerebellar Purkinje cells in the control group( P>0.05), and the coefficient of variation decreased compared to before administration ( t=6.95, P<0.05). After administering AMPA receptor antagonists on the surface of the brain, there were no significant changes in the discharge frequency and coefficient of variation in both the ethanol group and control group compared to before administration (both P>0.05). After simultaneously blocking AMPA and GABAA receptors, it was found that the spontaneous discharge frequency in ethanol group increased after administration compared to before administration((107.3±4.3)%, (99.7±3.7)%, P<0.05), and the increased value of frequency in the ethanol group was also higher than that of control group ( P<0.05). After simultaneously blocking AMPA and GABAA receptors, the coefficient of variation of the alcohol group and the control group mice were both lower than those before administration (both P<0.05), and the decrease in the alcohol group was higher than that in the control group ( P<0.05). Conclusion:Chronic ethanol exposure significantly inhibited the spontaneous discharge of Purkinje cells in the cerebellum, and the enhancement of inhibitory components was achieved by the inhibitory input mediated by GABAA receptors.

Ethanol is one of the most widely used and abused psychoactive substances in the world. Long-term and excessive intake of alcohol can damage the central nervous system and lead to impairment of its function. As an important component of the central nervous system, cerebellum is one of the main target organs damaged by ethanol. Acute and chronic ethanol intake can damage human motor coordination, motor learning and some cognitive functions. Its damage mechanism is generally believed to be caused by the abnormal function of cerebellar cortical neural circuit caused by ethanol intake. Combined with recent studies on the mouse model of long-term ethanol intake, this article reviews the cerebellar neural network mechanism of long-term ethanol intake from various aspects, with a view to providing research and development in behavioral movement, motor coordination, cognitive function, depression, and offers new ideas with the rise of precision medicine for treatment. People are increasingly interested in exploring the mechanism of long-term ethanol intake on the cerebellar neural network. How to improve or block the corresponding mechanism based on the mechanism of action found in existing research is an important proposition in future research.